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Sex-Specific Characteristics of the Microcirculation

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Sex-Specific Analysis of Cardiovascular Function

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1065))

Abstract

The requirements of metabolizing tissue are both continuous and variable; accordingly, the microvasculature serving that tissue must be similarly dynamic. Just as it is recognized that males and females of the same species have differing metabolic requirements, is it not likely that the microvasculature serving these tissues will differ by sex? This section focusing on the constituents of the microcirculation identifies what is known presently about the role sex plays in matching metabolic demand with microvascular function and areas requiring additional study. Many of the identified sex differences are subtle and easily ignored. In the aggregate, though, they can profoundly alter phenotype, especially under stressful conditions including pregnancy, exercise, and disease states ranging from diabetes to heart failure. Although the features presently identified to “have sex” range from differences in growth, morphology, protein expression, and intracellular signaling, males and females alike achieve homeostasis, likely by different means. Studies of microvascular sexual dimorphism are also identifying age as an independent but interacting factor requiring additional attention. Overall, attempting to ignore either sex and/or age is inappropriate and will prevent the design and implementation of appropriate interventions to present, ameliorate, or correct microvascular dysfunction.

Art work by Piet Michiels, Leuven, Belgium

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References

  1. Aanerud J, Borghammer P, Rodell A, Jónsdottir KY, Gjedde A. Sex differences of human cortical blood flow and energy metabolism. J Cereb Blood Flow Metab. 2017;37(7):2433–40. https://doi.org/10.1177/0271678X16668536.

    Article  PubMed  Google Scholar 

  2. Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res. 2007;100(2):158–73. https://doi.org/10.1161/01.RES.0000255691.76142.4a.

    Article  PubMed  CAS  Google Scholar 

  3. Ak G, Buyukberber S, Sevinc A, Turk HM, Ates M, Sari R, Savli H, Cigli A. The relation between plasma endothelin-1 levels and metabolic control, risk factors, treatment modalities, and diabetic microangiopathy in patients with Type 2 diabetes mellitus. J Diabetes Complicat. 2001;15(3):150–7. https://doi.org/10.1016/S1056-8727(01)00137-4.

    Article  PubMed  CAS  Google Scholar 

  4. Arnetz L, Ekberg N, Alvarsson M. Sex differences in type 2 diabetes: focus on disease course and outcomes. Diabetes Metab Syndr Obes Targets Ther. 2014;7:409–20.

    Article  Google Scholar 

  5. Augustin HG, Koh GY. Organotypic vasculature: from descriptive heterogeneity to functional pathophysiology. Science. 2017;2379(August):1–22. https://doi.org/10.1126/science.aal2379.

    Article  Google Scholar 

  6. Baatout S. Endothelial differentiation using Matrigel (review). Anticancer Res. 1997;17(1A):451–5. https://doi.org/10.2307/1276261.

    Article  PubMed  CAS  Google Scholar 

  7. Barnes JN. Sex specific factors regulating pressure and flow. Exp Physiol. 2017;102:1385. https://doi.org/10.1113/EP086531.

    Article  PubMed  Google Scholar 

  8. Bates DO. Vascular endothelial growth factors and vascular permeability. Cardiovasc Res. 2010;87(2):262–71. https://doi.org/10.1093/cvr/cvq105.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Casimir GJA, Duchateau J. Gender differences in inflammatory processes could explain poorer prognosis for males. J Clin Microbiol. 2011;49(1):478–9. https://doi.org/10.1128/JCM.02096-10.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Castle-Miller J, Bates DO, Tortonese DJ. Mechanisms regulating angiogenesis underlie seasonal control of pituitary function. Proc Natl Acad Sci U S A. 2017;114(12):E2514–23. https://doi.org/10.1073/pnas.1618917114.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Chen Q, Williams R, Healy CL, Wright CD, Wu SC, O’Connell TD. An association between gene expression and better survival in female mice following myocardial infarction. J Mol Cell Cardiol. 2010;49(5):801–11. https://doi.org/10.1016/j.yjmcc.2010.08.002.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Choi I, Lee S, Hong YK. The new era of the lymphatic system: no longer secondary to the blood vascular system. Cold Spring Harb Perspect Med. 2012;2(4):1–23. https://doi.org/10.1101/cshperspect.a006445.

    Article  CAS  Google Scholar 

  13. Dantas APV, Franco M d CP, Silva-Antonialli MM, Tostes RCA, Fortes ZB, Nigro D, Carvalho MHC. Gender differences in superoxide generation in microvessels of hypertensive rats: role of NAD(P)H-oxidase. Cardiovasc Res. 2004;61(1):22–9. https://doi.org/10.1016/j.cardiores.2003.10.010.

    Article  PubMed  CAS  Google Scholar 

  14. Davis CM, Fairbanks SL, Alkayed NJ. Mechanism of the sex difference in endothelial dysfunction after stroke. Transl Stroke Res. 2013;4(4):381–9. https://doi.org/10.1007/s12975-012-0227-0.

    Article  PubMed  Google Scholar 

  15. Diler AS, Üzüm G, Akgün Dar K, Aksu U, Atukeren P, Ziylan YZ. Sex differences in modulating blood brain barrier permeability by NO in pentylenetetrazol-induced epileptic seizures. Life Sci. 2007;80(14):1274–81. https://doi.org/10.1016/j.lfs.2006.12.039.

    Article  PubMed  CAS  Google Scholar 

  16. Dongaonkar RM, Stewart RH, Geissler HJ, Laine GA. Myocardial microvascular permeability, interstitial oedema, and compromised cardiac function. Cardiovasc Res. 2010;87(2):331–9. https://doi.org/10.1093/cvr/cvq145.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Duma D, Collins JB, Chou JW, Cidlowski JA. Sexually dimorphic actions of glucocorticoids provide a link to inflammatory diseases with gender differences in prevalence. Sci Signal. 2010;3(143):ra74. https://doi.org/10.1126/scisignal.2001077.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Duvekot JJ, Cheriex EC, Pieters FAA, Peeters PLH, Menheere LPCA. Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone. Am J Obstet Gynecol. 1993;169(6):1382–92. https://doi.org/10.1016/0002-9378(93)90405-8.

    Article  PubMed  CAS  Google Scholar 

  19. Ely D, Boehme S, Dunphy G, Hart M, Chiarappa F, Miller B, Martins AS, Turner M, Milsted A. The Sry3 Y chromosome locus elevates blood pressure and renin-angiotensin system indexes. Gend Med. 2011;8(2):126–38. https://doi.org/10.1016/j.genm.2010.11.014.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Eriksson M, Sartono E, Martins CL, Balé C, Garly ML, Whittle H, Aaby P, Pedersen BK, Yazdanbakhsh M, Erikstrup C, Benn CS. A comparison of ex vivo cytokine production in venous and capillary blood. Clin Exp Immunol. 2007;150:469–76. https://doi.org/10.1111/j.1365-2249.2007.03515.x.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Faber JE, Moore SM, Lucitti JL, Aghajanian A, Zhang H. Sex differences in the cerebral collateral circulation. Transl Stroke Res. 2017;8(3):273–83. https://doi.org/10.1007/s12975-016-0508-0.

    Article  PubMed  Google Scholar 

  22. Fall T, Hågg S, Ploner A, Mågi R, Fischer K, Draisma HHM, Sarin AP, Benyamin B, Ladenvall C, Åkerlund M, Kals M, Esko T, Nelson CP, Kaakinen M, Huikari V, Mangino M, Meirhaeghe A, Kristiansson K, Nuotio ML, Kobl M, Grallert H, Dehghan A, Kuningas M, De Vries PS, De Bruijn RFAG, Willems SM, Heikkila K, Silventoinen K, Pietilainen KH, Legry V, Giedraitis V, Goumidi L, Syvanen AC, Strauch K, Koenig W, Lichtner P, Herder C, Palotie A, Menni C, Uitterlinden AG, Kuulasmaa K, Havulinna AS, Moreno LA, Gonzalez-Gross M, Evans A, Tregouet DA, Yarnell JWG, Virtamo J, Ferrieres J, Veronesi G, Perola M, Arveiler D, Brambilla P, Lind L, Kaprio J, Hofman A, Stricker BH, Van Duijn CM, Ikram MA, Franco OH, Cottel D, Dallongeville J, Hall AS, Jula A, Tobin MD, Penninx BW, Peters A, Gieger C, Samani NJ, Montgomery GW, Whitfield JB, Martin NG, Groop L, Spector TD, Magnusson PK, Amouyel P, Boomsma DI, Nilsson PM, Jarvelin MR, Lyssenko V, Metspalu A, Strachan DP, Salomaa V, Ripatti S, Pedersen NL, Prokopenko I, Mccarthy MI, Ingelsson E. Age- and sex-specific causal effects of adiposity on cardiovascular risk factors. Diabetes. 2015;64(5):1841–52. https://doi.org/10.2337/db14-0988.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Franconi F, Rosano G, Basili S, Montella A, Campesi I. Human cells involved in atherosclerosis have a sex. Int J Cardiol. 2017;228(February):983–1001. https://doi.org/10.1016/j.ijcard.2016.11.118.

    Article  PubMed  Google Scholar 

  24. Freedman RR, Sabharwal SC, Desai N. Sex differences in peripheral vascular adrenergic receptors. Circ Res. 1987;61:581–7.

    Article  CAS  PubMed  Google Scholar 

  25. Friedrich V, Bi W, Sehba FA. Sexual dimorphism in gene expression after aneurysmal subarachnoid hemorrhage. Neurol Res. 2015;37(12):1054–9. https://doi.org/10.1080/01616412.2015.1115211.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Galipeau D, Verma S, McNeill JH. Female rats are protected against fructose-induced changes in metabolism and blood pressure. Am J Physiol Heart Circ Physiol. 2002;283(6):H2478–84. https://doi.org/10.1152/ajpheart.00243.2002.

    Article  PubMed  CAS  Google Scholar 

  27. Asellius G. De lactibus sive lacteis venis. Milan: Mediolani; 1627.

    Google Scholar 

  28. Gill SE, Taneja R, Rohan M, Wang L, Mehta S. Pulmonary microvascular albumin leak is associated with endothelial cell death in murine sepsis-induced lung injury in vivo. PLoS One. 2014;9(2):1–12. https://doi.org/10.1371/journal.pone.0088501.

    Article  CAS  Google Scholar 

  29. Gillis EE, Sasser JM, Sullivan JC. Endothelin, sex, and pregnancy: unique considerations for blood pressure control in females. Am J Phys Regul Integr Comp Phys. 2016;310(8):691–6. https://doi.org/10.1152/ajpregu.00427.2015.

    Article  Google Scholar 

  30. Glinskii OV, Abraha TW, Turk JR, Rubin LJ, Huxley VH, Glinsky VV. Microvascular network remodeling in dura mater of ovariectomized pigs: role for angiopoietin-1 in estrogen-dependent control of vascular stability. Am J Physiol Heart Circ Physiol. 2007;293(2):H1131–7. https://doi.org/10.1152/ajpheart.01156.2006.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Glinskii OV, Huxley VH, Glinskii VV, Rubin LJ, Glinsky VV. Pulsed estrogen therapy prevents post-OVX porcine dura mater microvascular network weakening via a PDGF-BB-dependent mechanism. PLoS One. 2013;8(12):1–9. https://doi.org/10.1371/journal.pone.0082900.

    Article  CAS  Google Scholar 

  32. Gohar EY, Giachini FR, Pollock DM, Tostes RCA. Role of the endothelin system in sexual dimorphism in cardiovascular and renal diseases. Life Sci. 2016a;159:20–9. https://doi.org/10.1016/j.lfs.2016.02.093. Elsevier Inc

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Gohar EY, Yusuf C, Pollock DM. Ovarian hormones modulate endothelin A and B receptor expression. Life Sci. 2016b;159:148–52. https://doi.org/10.1016/j.lfs.2016.01.010. Elsevier Inc

    Article  PubMed  CAS  Google Scholar 

  34. Gonzales RJ, Bryant JM, Naik JS, Resta TC, Walker BR. Gender differences in mesenteric vasoconstrictor reactivity following chronic hypoxia. Microcirculation. 2008;15(6):473–84. https://doi.org/10.1080/10739680801891348.

    Article  PubMed  CAS  Google Scholar 

  35. Grines CL. Acute coronary syndromes: acute MI in women – the fountain of youth has run dry. Nat Rev Cardiol. 2015;12(6):322–3. https://doi.org/10.1038/nrcardio.2015.66.. Nature Publishing Group

    Article  PubMed  Google Scholar 

  36. Hack CE, Zeerleder S. The endothelium in sepsis: source of and a target for inflammation. Crit Care Med. 2001;29(7 Suppl):S21–7. https://doi.org/10.1097/00003246-200107001-00011.

    Article  PubMed  CAS  Google Scholar 

  37. Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, O’Farrell FM, Buchan AM, Lauritzen M, Attwell D. Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 2014;508(7494):55–60. https://doi.org/10.1038/nature13165.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Harm DL, Jennings RT, Meck JV, Powell MR, Putcha L, Sams CP, Schneider SM, Shackelford LC, Smith SM, Whitson PA. Invited review: gender issues related to spaceflight: a NASA perspective. J Appl Physiol. 2001;91:2374–83.

    Article  CAS  PubMed  Google Scholar 

  39. Hart EC, Charkoudian N,Wallin BG, Curry TB, Eisenach J, Joyner MJ. Sex and ageing differences in resting arterial pressure regulation: the role of the beta-adrenergic receptors. J Physiol. 2011, 589:5285–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. He J, Gu D, Chen J, Jaquish CE, Rao DC, Hixson JE, Chen J, Duan X, Huang J, Chen C-S, Kelly TN, Bazzano LA, Whelton PK. Gender difference in blood pressure responses to dietary sodium intervention in the GenSalt study. J Hypertens. 2009;27(1):48–54. https://doi.org/10.1097/HJH.0b013e328316bb87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. He P. Leucocyte/endothelium interactions and microvessel permeability: coupled or uncoupled? Cardiovasc Res. 2010;87(2):281–90. https://doi.org/10.1093/cvr/cvq140.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Huang A, Sun D, Koller A, Kaley G. Gender difference in myogenic tone of rat arterioles is due to estrogen-induced, enhanced release of NO. Am J Physiol Heart Circ Physiol. 1997;272(4 Pt 2):H1804–9.

    Article  CAS  Google Scholar 

  43. Huxley VH. Physiologic regulation of capillary permeability. J Reconstr Microsurg. 1988a;4(4):341–6.

    Article  CAS  PubMed  Google Scholar 

  44. Huxley VH, Curry F-RE. Albumin modulation of capillary permeability: test of an adsorption mechanism. Am J Physiol Heart Circ Physiol. 1985;248(2 Pt 2):H264–73.

    Article  CAS  Google Scholar 

  45. Huxley VH, Curry FE, Powers MR, Thipakorn B. Differential action of plasma and albumin on transcapillary exchange of anionic solute. Am J Physiol Heart Circ Physiol. 1993a;264:H1428–37.

    Article  CAS  Google Scholar 

  46. Huxley, V. H., McKay, M. K., Meyer Jr., D. J., Williams, D. A. and Zhang, R. S. (1993b) ‘Vasoactive hormones and autocrine activation of capillary exchange barrier function.’, Blood Cells, 19(2), pp. 309–20–4.

    Google Scholar 

  47. Huxley VH, Meyer DJ Jr. Atrial natriuretic peptide (ANP)-induced increase in capillary albumin and water flux. Adv Exp Med Biol. 1988;242:23–31.

    Article  CAS  PubMed  Google Scholar 

  48. Huxley VH, Meyer DJ Jr. Capillary permeability: an albumin component attenuates active changes in Lp. Am J Physiol Heart Circ Physiol. 1990a;259(5 Pt 2):H1357–64.

    Article  CAS  Google Scholar 

  49. Huxley VH, Meyer DJ Jr. Capillary permeability: atrial peptide action is independent of “protein effect”. Am J Physiol Heart Circ Physiol. 1990b;259(5 Pt 2):H1351–6.

    Article  CAS  Google Scholar 

  50. Huxley VH, Sieveking S, Kemp S, Schramm C. Phenotypic sexual dimorphism of micro- and macrovascular endothelium with respect to size, growth, and wound repair. FASEB J. 2017;31(Suppl 1.) p. 678.14

    Google Scholar 

  51. Huxley VH, Tucker VL, Verburg KM, Freeman RH. Increased capillary hydraulic conductivity induced by atrial natriuretic peptide. Circ Res. 1987;60(2):304–7. https://doi.org/10.1161/01.RES.60.2.304.

    Article  PubMed  CAS  Google Scholar 

  52. Huxley VH, Wang J. Cardiovascular sex differences influencing microvascular exchange. Cardiovasc Res. 2010;87(2):230–42. https://doi.org/10.1093/cvr/cvq142.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Huxley VH, Wang JJ, Sarelius IH. Adaptation of coronary microvascular exchange in arterioles and venules to exercise training and a role for sex in determining permeability responses. Am J Physiol Heart Circ Physiol. 2007;293(2):H1196–205. https://doi.org/10.1152/ajpheart.00069.2007.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Huxley VH, Wang J, Whitt SP. Sexual dimorphism in the permeability response of coronary microvessels to adenosine. Am J Physiol Heart Circ Physiol. 2004;288(4):H2006–13. https://doi.org/10.1152/ajpheart.01007.2004.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Huxley VH, Williams DA. Role of a glycocalyx on coronary arteriole permeability to proteins: evidence from enzyme treatments. Am J Physiol Heart Circ Physiol. 2000;278(4):H1177–85.

    Article  CAS  PubMed  Google Scholar 

  56. Jacob M, Saller T, Chappell D, Rehm M, Welsch U, Becker BF. Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability. Basic Res Cardiol. 2013;108(347):1–9. https://doi.org/10.1007/s00395-013-0347-z.

    Article  Google Scholar 

  57. Joyner MJ, Casey DP. Regulation of increased blood flow (hyperemia) to muscles during exercise: a hierarchy of competing physiological needs. Physiol Rev. 2015;95(2):549–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kassab GS, Rider CA, Tang NJ, Fung YC. Morphometry of pig coronary arterial trees. Am J Physiol Heart Circ Physiol. 1993;265(1):H3350–H365.

    Google Scholar 

  59. Kastrup A, Dichgans J, Niemeier M, Schabet M. Changes of cerebrovascular CO2 reactivity during normal aging. Stroke. 1998;29:1311–4. https://doi.org/10.1161/01.STR.29.7.1311.

    Article  PubMed  CAS  Google Scholar 

  60. Kaufman MJ, Levin JM, Maas LC, Kukes TJ, Villafuerte RA, Dostal K, Lukas SE, Mendelson JH, Cohen BM, Renshaw PF. Cocaine-induced cerebral vasoconstriction differs as a function of sex and menstrual cycle phase. Biol Psychiatry. 2001;49(9):774–81. https://doi.org/10.1016/S0006-3223(00)01091-X.

    Article  PubMed  CAS  Google Scholar 

  61. Kautzky-Willer A, Harreiter JJ, Pacini G. Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. Endocr Rev. 2016;37(3):278–316. https://doi.org/10.1210/er.2015-1137.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Kimura K, Hashiguchi T, Deguchi T, Horinouchi S, Uto T, Oku H, Setoyama S, Maruyama I, Osame M, Arimura K. Serum VEGF—as a prognostic factor of atherosclerosis. Atherosclerosis. 2007;194:182–8. https://doi.org/10.1016/j.atherosclerosis.2006.07.025.

    Article  PubMed  CAS  Google Scholar 

  63. Kneale BJ, Chowienczyk PJ, Brett SE, Coltart DJ, Ritter JM. Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature. J Am Coll Cardiol. 2000; 36:1233–8.

    Article  CAS  PubMed  Google Scholar 

  64. Kovats S. Estrogen receptors regulate innate immune cells and signaling pathways. Cell Immunol. 2015;294:63–9. https://doi.org/10.1016/j.cellimm.2015.01.018.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Krogh A. The anatomy and physiology of capillaries. New Haven: Yale University Press; 1922.

    Google Scholar 

  66. LeBlanc AJ, Chen B, Dougherty PJ, Reyes RA, Shipley RD, Korzick DH, Muller-Delp JM. Divergent effects of aging and sex on vasoconstriction to endothelin in coronary arterioles. Microcirculation. 2013;20(5):365–76. https://doi.org/10.1111/micc.12028.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. LeBlanc AJ, Nevitt CD. Targeting the vessel underdogs: therapeutic approaches for microvessel dysfunction in the heart. Crit Rev Biomed Eng. 2015;43(5–6):473–89. https://doi.org/10.1615/CritRevBiomedEng.2016016083.

    Article  PubMed  Google Scholar 

  68. Levi M, Van Der Poll T. Endothelial injury in sepsis. Intensive Care Med. 2013;39:1839–42. https://doi.org/10.1007/s00134-013-3054-1.

    Article  PubMed  Google Scholar 

  69. Liu W, Lou X, Ma L. Use of 3D pseudo-continuous arterial spin labeling to characterize sex and age differences in cerebral blood flow. Neuroradiology. 2016;58(9):943–8. https://doi.org/10.1007/s00234-016-1713-y.

    Article  PubMed  Google Scholar 

  70. Lukasz A, Hillgruber C, Oberleithner H, Kusche-Vihrog K, Pavenstädt H, Rovas A, Hesse B, Goerge T, Kümpers P. Endothelial glycocalyx breakdown is mediated by angiopoietin-2. Cardiovasc Res. 2017;113(6):671–80. https://doi.org/10.1093/cvr/cvx023.

    Article  PubMed  Google Scholar 

  71. MacIntyre JN, Slusar JE, Zhu J, Dong AX, Howlett SE, Kelly ME. Age-associated alterations in retinal arteriole reactivity to endothelin-1 differ between the sexes. Mech Ageing Dev. 2012;133(9–10):611–9. https://doi.org/10.1016/j.mad.2012.08.001.

    Article  PubMed  CAS  Google Scholar 

  72. Macintyre S, Hunt K, Sweeting H. Gender differences in health: are things really as simple as they seem? Soc Sci Med. 1996;42(4):617–24. https://doi.org/10.1016/0277-9536(95)00335-5.

    Article  PubMed  CAS  Google Scholar 

  73. Madri JA, Williams SK, Wyatt T, Mezzlo C. Capillary endothelial cell by matrix components cultures: phenotypic modulation by matrix components. J Cell Biol. 1983;97:153–65.

    Article  CAS  PubMed  Google Scholar 

  74. Maggioli E, McArthur S, Mauro C, Kieswich J, Kusters DHM, Reutelingsperger CPM, Yaqoob M, Solito E. Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking. Brain Behav Immun. 2015;51:212–22. https://doi.org/10.1016/j.bbi.2015.08.020.

    Article  PubMed  Google Scholar 

  75. Mark S, Scott GBI, Donoviel DB, Leveton LB, Mahoney E, Charles JB, Siegel B. The impact of sex and gender on adaptation to space: executive summary. J Women's Health (Larchmt). 2014;23(11):941–7. https://doi.org/10.1089/jwh.2014.4914.

    Article  Google Scholar 

  76. Martinez-Lemus, L. A. (2011) ‘MiniReview The dynamic structure of arterioles’, Basic & Clinical Pharmacology & Toxicology, 110, pp. 5–11. doi: https://doi.org/10.1111/j.1742-7843.2011.00813.x.

    Article  Google Scholar 

  77. McKay MK, Huxley VH. ANP increases capillary permeability to protein independent of perfusate protein composition. Am J Physiol Heart Circ Physiol. 1995;268(3 Pt 2):H1139–48.

    Article  CAS  Google Scholar 

  78. Miller VM, Garovic VD, Kantarci K, Barnes JN, Jayachandran M, Mielke MM, Joyner MJ, Shuster LT, Rocca WA. Sex-specific risk of cardiovascular disease and cognitive decline: pregnancy and menopause. Biol Sex Differ. 2013;4(1):6. https://doi.org/10.1186/2042-6410-4-6.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Miranda CH, de Carvalho Borges M, Schmidt A, Marin-Neto JA, Pazin-Filho A. Evaluation of the endothelial glycocalyx damage in patients with acute coronary syndrome. Atherosclerosis. 2016;247:184–8. https://doi.org/10.1016/j.atherosclerosis.2016.02.023.

    Article  PubMed  CAS  Google Scholar 

  80. Mudrovcic, N., Arefin, S., Van Craenenbroeck, A. H. and Kublickiene, K. (2017) Endothelial maintenance in health and disease: importance of sex differences Pharmacol Res 119, pp. 48–60. doi: https://doi.org/10.1016/j.phrs.2017.01.011.

    Article  PubMed  CAS  Google Scholar 

  81. Muller-Delp JM. The coronary microcirculation in health and disease. Physiology. 2013;2013:1–24. https://doi.org/10.1155/2013/238979.

    Article  Google Scholar 

  82. Murthy VL, Naya M, Taqueti VR, Foster CR, Gaber M, Hainer J, Dorbala S, Blankstein R, Rimoldi O, Camici PG, Di Carli MF. Effects of sex on coronary microvascular dysfunction and cardiac outcomes. Circulation. 2014;129(24):2518–27. https://doi.org/10.1161/CIRCULATIONAHA.113.008507.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Nathan L, Pervin S, Singh R, Rosenfeld M, Chaudhuri G. Estradiol inhibits leukocyte adhesion and transendothelial migration in rabbits in vivo: possible mechanisms for gender differences in atherosclerosis. Circ Res. 1999;85(4):377–85. https://doi.org/10.1161/01.RES.85.4.377.

    Article  PubMed  CAS  Google Scholar 

  84. Nussbaum C, Cavalcanti Fernandes Heringa A, Mormanova Z, Puchwein-Schwepcke AF, Bechtold-Dalla Pozza S, Genzel-Boroviczény O. Early microvascular changes with loss of the glycocalyx in children with type 1 diabetes. J Pediatr. 2014;164(3):584–9. https://doi.org/10.1016/j.jpeds.2013.11.016.

    Article  PubMed  Google Scholar 

  85. O’Farrell FM, Attwell D. A role for pericytes in coronary no-reflow. Nat Rev Cardiol. 2014;11(7):427–32. https://doi.org/10.1038/nrcardio.2014.58.

    Article  PubMed  Google Scholar 

  86. Oertelt-Prigione S, Regitz-Zagrosek V. Gender aspects in cardiovascular pharmacology. J Cardiovasc Transl Res. 2009;2(3):258–66. https://doi.org/10.1007/s12265-009-9114-9.

    Article  PubMed  Google Scholar 

  87. Olyslaegers DA, Desmarets LM, Dedeurwaerder A, Dewerchin HL, Nauwynck HJ. Generation and characterization of feline arterial and venous endothelial cell lines for the study of the vascular endothelium. BMC Vet Res. 2013;9(1):170. https://doi.org/10.1186/1746-6148-9-170.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Pak KJ, Geary GG, Duckles SP, Krause DN. Male–female differences in the relative contribution of endothelial vasodilators released by rat tail artery. Life Sci. 2002;71:1633–42.

    Article  CAS  PubMed  Google Scholar 

  89. Panazzolo DG, Da Silva LHA, Cyrino FZGDA, Sicuro FL, Kraemer-Aguiar LG, Bouskela E. Gender differences in microcirculation: observation using the hamster cheek pouch. Clinics (Sao Paulo). 2013;68(12):1537–42. https://doi.org/10.6061/clinics/2013(12)10.

    Article  Google Scholar 

  90. Papanek PE, Rieder MJ, Lombard JH, Greene AS. Gender-specific protection from microvessel rarefaction in female hypertensive rats. Am J Hypertension 1998;11(8 I):998–1005. https://doi.org/10.1016/S0895-7061(98)00114-9.

    Article  CAS  PubMed  Google Scholar 

  91. Patel H, Rosengren A, Ekman I. Symptoms in acute coronary syndromes: does sex make a difference? Am Heart J. 2004;148:27–33. https://doi.org/10.1016/j.ahj.2004.03.005.

    Article  PubMed  Google Scholar 

  92. Patel MB, Bui LP, Kirkeeide RL, Gould KL. Imaging microvascular dysfunction and mechanisms for female-male differences in CAD. J Am Coll Cardiol Img. 2016;9(4):465–82. https://doi.org/10.1016/j.jcmg.2016.02.003.

    Article  Google Scholar 

  93. Peters SAE, Huxley RR, Woodward M. Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775,385 individuals and 12,539 strokes. Lancet. 2014;383(9933):1973–80. https://doi.org/10.1016/S0140-6736(14)60040-4.

    Article  PubMed  Google Scholar 

  94. Pietropaoli AP, Glance LG, Oakes D, Fisher SG. Gender differences in mortality in patients with severe sepsis or septic shock. Gend Med. 2010;7(5):422–37. https://doi.org/10.1016/j.genm.2010.09.005.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Reckelhoff JF. Gender differences in the regulation of blood pressure. J Am Heart Assoc. 2001;37:1199–208. https://doi.org/10.1161/01.HYP.37.5.1199.

    Article  CAS  Google Scholar 

  96. Regan, E. R. and Aird, W. C. (2012) ‘Dynamical systems approach to endothelial heterogeneity.’, Circ Res, 111(1), pp. 110–130. doi: https://doi.org/10.1161/CIRCRESAHA.111.261701.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Rhodin JAG. The ultrastructure of mammalian arterioles and precapillary sphincters. J Ultrastruct Res. 1967;18(1–2):181–223. https://doi.org/10.1016/S0022-5320(67)80239-9.

    Article  PubMed  CAS  Google Scholar 

  98. Rhodin JAG. Ultrastructure of mammalian venous capillaries, venules, and small collecting veins. J Ultrastruct Res. 1968;25(5):452–500.

    Article  CAS  PubMed  Google Scholar 

  99. Roy-O’Reilly M, McCullough LD. Sex differences in stroke: the contribution of coagulation. Exp Neurol. 2014;259:16–27. https://doi.org/10.1016/j.expneurol.2014.02.011.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Sadrzadeh Rafie AH, Stefanick ML, Sims ST, Phan T, Higgins M, Gabriel A, Assimes T, Narasimhan B, Nead KT, Myers J, Olin J, Cooke JP. Sex differences in the prevalence of peripheral artery disease in patients undergoing coronary catheterization. Vasc Med. 2010;15(6):443–50. https://doi.org/10.1177/1358863X10388345.

    Article  PubMed  Google Scholar 

  101. Sage H, Pritzl P, Bornstein P. Secretory phenotypes of endothelial cells in culture: comparison of aortic, venous, capillary, and corneal endothelium. Arterioscler Thromb Vasc Biol. 1981;1(6):427–42. https://doi.org/10.1161/01.ATV.1.6.427.

    Article  CAS  Google Scholar 

  102. Salmon AH, Satchell SC. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. J Pathol. 2012;226(4):562–74. https://doi.org/10.1002/path.3964.

    Article  PubMed  CAS  Google Scholar 

  103. Sasaki R. Roles of sex and insulin on microvascular exchange function. Columbia: University of Missouri; 2007.

    Google Scholar 

  104. Sasaki R, Whitt SP, Huxley VH. Permeability response of the rat mesenteric microvasculature to insulin. Clin Hemorheol Microcirc. 2006;34(1–2):259–63.

    PubMed  PubMed Central  CAS  Google Scholar 

  105. Scallan JP, Huxley VH, Korthuis RJ. Capillary fluid exchange regulation, functions, and pathology, colloquium series on integrated systems physiology: from molecule to function. San Rafael: Morgan & Claypool Life Sciences; 2010.

    Google Scholar 

  106. Schröder J, Kahlke V, Staubach KH, Zabel P, Stüber F. Gender differences in human sepsis. Arch Surg. 1998;133(11):1200–5. https://doi.org/10.1001/archsurg.133.11.1200.

    Article  PubMed  Google Scholar 

  107. Schuetz P, Yano K, Sorasaki M, Ngo L, St Hilaire M, Lucas JM, Aird WC, Shapiro NI. Influence of diabetes on endothelial cell response during sepsis. Diabetologia. 2011;54(5):996–1003. https://doi.org/10.1007/s00125-011-2059-y.

    Article  PubMed  CAS  Google Scholar 

  108. Schwertz D, Penckofer S. Sex differences and the effects of sex hormones on hemostasis and vascular reactivity. Heart Lung J Crit Care. 2001;30(6):401–26. https://doi.org/10.1067/mhl.2001.118764.

    Article  CAS  Google Scholar 

  109. Segal JB, Moliterno AR. Platelet counts differ by sex, ethnicity, and age in the United States. Ann Epidemiol. 2006;16(2):123–30. https://doi.org/10.1016/j.annepidem.2005.06.052.

    Article  PubMed  Google Scholar 

  110. Sharawy N, Ribback S, Al-Banna N, Lehmann C, Kern H, Wendt M, Cerny V, Dombrowski F, Pavlovic D. Estradiol receptors agonists induced effects in rat intestinal microcirculation during sepsis. Microvasc Res. 2013;85:118–27. https://doi.org/10.1016/j.mvr.2012.10.002.

    Article  PubMed  CAS  Google Scholar 

  111. Shore AC, Sandeman DD, Tooke JE. Capillary pressure, pulse pressure amplitude, and pressure waveform in healthy volunteers. Am J Physiol Heart Circ Physiol. 1995;268(1):H147–54.

    Article  CAS  Google Scholar 

  112. Siamwala JH, Macias BR, Lee PC, Hargens AR. Gender differences in tibial microvascular flow responses to head down tilt and lower body negative pressure. Phys Rep. 2017;5(4):e13143. https://doi.org/10.14814/phy2.13143.

    Article  Google Scholar 

  113. Sorop O, Olver TD, Van DeWouw J, Heinonen I, Van Duin RW, Duncker DJ, Merkus D. The microcirculation: a key player in obesity-associated cardiovascular disease. Cardiovasc Res. 2017;113(9):1035–45. https://doi.org/10.1093/cvr/cvx093.

    Article  PubMed  Google Scholar 

  114. Sullivan JC, Rodriguez-Miguelez P, Zimmerman MA, Harris RA. Differences in angiotensin (1–7) between men and women. Am J Physiol Heart Circ Physiol. 2015;308(9):H1171–6. https://doi.org/10.1152/ajpheart.00897.2014.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Sun H, Mayhan WG. Sex difference in nitric oxide synthase-dependent dilatation of cerebral arterioles during long-term alcohol consumption. Alcohol Clin Exp Res. 2005;29(3):430–6. https://doi.org/10.1097/01.ALC.0000156117.87892.22.

    Article  PubMed  CAS  Google Scholar 

  116. Szabó A, Vollmar B, Boros M, Menger MD. Gender differences in ischemia-reperfusion-induced microcirculatory and epithelial dysfunctions in the small intestine. Life Sci. 2006;78(26):3058–65. https://doi.org/10.1016/j.lfs.2005.12.012.

    Article  PubMed  CAS  Google Scholar 

  117. Thurston G, Baluk P, McDonald D. Determinants of endothelial cell phenotype in venules. Microcirculation. 2000;7(1):67–80. https://doi.org/10.1111/j.1549-8719.2000.tb00743.x.

    Article  PubMed  CAS  Google Scholar 

  118. Tipton AJ, Sullivan JC. Sex differences in T cells in hypertension. Clin Ther. 2014;36(12):1822–900. https://doi.org/10.1016/j.clinthera.2014.07.011. Elsevier

    Article  CAS  Google Scholar 

  119. Tostes RCA, David FL, Carvalho MHC, Nigro D, Scivoletto R, Fortes ZB. Gender differences in vascular reactivity to endothelin-1 in deoxycorticosterone-salt hypertensive rats. J Cardiovasc Pharmacol. 2000;36(5 Suppl 1):S99–101.

    Article  CAS  PubMed  Google Scholar 

  120. Tostes RCA, Fortes ZB, Callera GE, Montezano AC, Touyz RM, Webb RC, Carvalho MHC. Endothelin, sex and hypertension. Clin Sci. 2008;114(2):85–97. https://doi.org/10.1042/CS20070169.

    Article  PubMed  CAS  Google Scholar 

  121. Wang J. Modulation of coronary and skeletal muscle exchange by Adensoine: role of adenosine receptors. Columbia: University of Missouri; 2005.

    Google Scholar 

  122. Wang J, Bingaman S, Huxley VH. Intrinsic sex-specific differences in microvascular endothelial cell phosphodiesterases. Am J Physiol Heart Circ Physiol. 2010;298(4):H1146–54. https://doi.org/10.1152/ajpheart.00252.2009.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Wang J, Whitt SP, Rubin LJ, Huxley VH. Differential coronary microvascular exchange responses to adenosine: roles of receptor and microvessel subtypes. Microcirculation (New York, NY: 1994). 2005;12(4):313–26. https://doi.org/10.1080/10739680590934736.

    Article  CAS  Google Scholar 

  124. Wolf MB. A three-pathway pore model describes extensive transport data from mammalian microvascular beds and frog microvessels. Microcirculation. 2002;9:497–511. https://doi.org/10.1038/sj.mn.7800163.

    Article  PubMed  Google Scholar 

  125. Wu NZ, Baldwin AL. Transient venular permeability increase and endothelial gap formation induced by histamine. Am J Physiol Heart Circ Physiol. 1992;262(4 Pt 2):H1238–47.

    Article  CAS  Google Scholar 

  126. Wu Y, Huang A, Sun D, Falck JR, Koller A, Kaley G. Gender-specific compensation for the lack of NO in the mediation of flow-induced arteriolar dilation. Am J Physiol Heart Circ Physiol. 2001;280:H2456–61.

    Article  CAS  PubMed  Google Scholar 

  127. Zimmerman MA, Sullivan JC. Hypertension: What’s sex got to do with it? Physiology. 2013;28:234–44. https://doi.org/10.1152/physiol.00013.2013.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Huxley, V.H., Kemp, S.S. (2018). Sex-Specific Characteristics of the Microcirculation. In: Kerkhof, P., Miller, V. (eds) Sex-Specific Analysis of Cardiovascular Function. Advances in Experimental Medicine and Biology, vol 1065. Springer, Cham. https://doi.org/10.1007/978-3-319-77932-4_20

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