{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:23:00Z","timestamp":1787016180634,"version":"build-2736575974"},"reference-count":91,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2018,7,15]],"date-time":"2018-07-15T00:00:00Z","timestamp":1531612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Endothelial dysfunction is an early hallmark of multiple disease states that also display sex differences with respect to age of onset, frequency and severity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Results of\n                            <jats:italic>in vivo<\/jats:italic>\n                            studies of basal and stimulated microvascular barrier function revealed sex differences that are difficult to ascribe to specific cells or environmental factors.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The present study evaluated endothelial cells (EC) isolated from macro\u2010 and\/or microvessels of reproductively mature rats under the controlled conditions of low\u2010passage culture aiming to test the assumption that EC phenotype would be sex independent.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The primary finding was that EC, regardless of where they are derived, retain a sex\u2010bias in low\u2010passage culture, independent of varying levels of reproductive hormones. The implications of the present study include the fallacy of expecting a universal set of mechanisms derived from study of EC from one sex and\/or one vascular origin to apply uniformly to all EC under unstimulated conditions, and no less in disease.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Vascular endothelial cells (EC) are heterogeneous with respect to phenotype, reflecting at least the organ of origin, location within the vascular network and physical forces. As an independent influence on EC functions in health or aetiology, susceptibility, and progression of dysfunction in numerous disease states, sex has been largely ignored. The present study focussed on EC isolated from aorta (macrovascular) and skeletal muscle vessels (microvascular) of age\u2010matched male and female rats under identical conditions of short\u2010term (passage 4) culture. We tested the hypothesis that genomic sex would not influence endothelial growth, wound healing, morphology, lactate production, or messenger RNA and protein expression of key proteins (sex hormone receptors for androgen and oestrogens \u03b1 and \u03b2; platelet endothelial cell adhesion molecule\u20101 and vascular endothelial cadherin mediating barrier function; \u03b1\n                      <jats:sub>v<\/jats:sub>\n                      \u03b2\n                      <jats:sub>3<\/jats:sub>\n                      and N\u2010cadherin influencing matrix interactions; intracellular adhesion molecule\u20101 and vascular cell adhesion molecule\u20101 mediating EC\/white cell adhesion). The hypothesis was rejected because the EC origin (macro\u2010\n                      <jats:italic>vs<\/jats:italic>\n                      . microvessel) and sex influenced multiple phenotypic characteristics. Statistical model analysis of EC growth demonstrated an hierarchy of variable importance, recapitulated for other phenotypic characteristics, with predictions assuming EC homogeneity\u00a0&lt;\u00a0sex\u00a0&lt;\u00a0vessel origin\u00a0&lt;\u00a0sex and vessel origin. Furthermore, patterns of EC mRNA expression by vessel origin and by sex did not predict protein expression. Overall, the present study demonstrated that accurate assessment of sex\u2010linked EC dysfunction first requires an understanding of EC function by position in the vascular tree and by sex. The results from a single EC tissue source\/species\/sex cannot provide universal insight into the mechanisms regulating\n                      <jats:italic>in vivo<\/jats:italic>\n                      endothelial function in health, and no less in disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp276048","type":"journal-article","created":{"date-parts":[[2018,6,9]],"date-time":"2018-06-09T08:05:15Z","timestamp":1528531515000},"page":"3929-3949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Sex differences influencing micro\u2010 and macrovascular endothelial phenotype\n                    <i>in vitro<\/i>"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6304-1617","authenticated-orcid":false,"given":"Virginia H.","family":"Huxley","sequence":"first","affiliation":[{"name":"National Center for Gender Physiology University of 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