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Endothelial Cell Barrier Protein Expression Differs by Organ and Sex
Author(s) -
Kemp Scott S.,
Huxley Virginia H,
Schramm Christine,
Sieveking Steven W
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.679.7
Subject(s) - biology , testis determining factor , vcam 1 , skeletal muscle , medicine , microbiology and biotechnology , endocrinology , cell adhesion molecule , gene , andrology , genetics , icam 1 , y chromosome
In both humans and animals, while functional sex differences have been observed, the mechanisms responsible for these differences remains poorly understood. Hypotheses include exposure to reproductive hormones, DNA preprogramming, or a combination of the two. Our goal is to elucidate the molecular mechanisms responsible for observed sex differences in basal and activated barrier function of adult rat microvessels. To this end we focused on cells isolated from age‐matched reproductively mature male and female rats (Sprague Dawley) to test the null hypothesis that protein expression does not differ by sex. Vascular cells were isolated from aorta and skeletal muscle to facilitate answering our question and compare our findings with previously published and observed data. Six markers associated with barrier function were chosen for study, CD 31 (PECAM‐1), α v β 3 (Integrin), N‐cadherin (CDH2), NCAM1 (CD 56), VCAM‐1 (CD 106), and ICAM‐1 (CD 54). Using flow cytometry we compared the difference in expression of these markers in sex‐verified (SRY gene expression) macro‐ and microvascular cells maintained in identical conditions of culture (Passage 8). Our current data suggests sex differences in aortic EC barrier proteins: α v β 3 , VCAM, NCAM and NCAD, with little to no sex difference observed in ICAM and CD 31. Sex differences have also been observed in the skeletal muscle EC barrier proteins: ICAM, VCAM, NCAM, with little to no difference observed in α v β 3 , NCAD and CD 31. Organ differences have been observed between skeletal muscle and aortic EC barrier proteins in ICAM, VCAM, NCAM and NCAD, with little difference observed in α v β 3 , and CD 31. Given that the proteins forming the junctional complex and regulating adhesion to the extracellular matrix differ between males and females we possess an initial understanding of one mechanism whereby barrier function may vary by sex under basal conditions. Future studies will focus on the 2 nd messenger pathways linked to these proteins and expression of proteins in these cells following exposure to vasoactive components shown to alter barrier function in a sexually dimorphic manner. Support or Funding Information NIH R01 DK095501