Aortic Endothelial Cells and Smooth Muscle Cells uncover mechanisms behind Atherosclerosis, Inflammation, Vascular Disease and Cardioprotection

Intimal hyperplasia, a vessel thickening seen in atherosclerosis, is common after vascular injury, angioplasty or bypass surgery. Such insults trigger proliferation and migration of vascular smooth muscle cells, creating a lesion. Studies suggest testosterone protects men from atherosclerotic cardiovascular disease and plaque formation. This sex steroid mainly acts via the androgen receptor (AR), expressed in endothelial & vascular smooth muscle cells. Wilhelmson and co-workers from the University of Gothenburg recently offered new insights on the topic. Published in the journal Endocrinology (2016), they show testosterone inhibits migration and proliferation of Human Aortic Smooth Muscle Cells (HAOSMC). The in vitro data supports in vivo observations, suggesting deficiency of the testosterone receptor AR may increase intimal hyperplasia. Testosterone supplementation, which continues to increase in elderly men, appears to offer some levels of cardiovascular protection. This study supports the contention that additional mechanisms, such as direct effects on the vascular wall by androgens, could play important roles in cardioprotection. Future research may uncover potential therapeutic roles for selective androgen modulators.

During extravasation, circulating granulocytes reach sites of infection and inflammation. Pathogens trigger expression of adhesion molecules, initiating the rolling and adhesion of neutrophils to the vascular endothelial lining. One of these adhesion molecules, the glycoprotein P-selectin (SELP), transports to the endothelial cell surface. There, SELP mediates rolling by binding to its ligand on the neutrophil surface. In a recent study from Research in Veterinary Science, Chen and colleagues find that activation of Bovine Aortic Endothelial Cells (BAOEC) enhances SELP-mediated leukocyte attachment. The study provides novel evidence that high SELP polymorphism rates may potentially influence not only leukocyte migration, but also fertility. Both processes are key to successful performance in dairy breeds. Some aspects from this study in bovines could translate to humans, where P Selectin gene polymorphisms are associated with pregnancy loss. Further work may deduce whether such gene changes influence immunity, fertility, embryo and placental development.

The protein Adiponectin, produced by perivascular adipose tissue and detected in plasma, helps thwart vascular disease. Adinopectin improves insulin sensitivity and coronary blood flow, and safeguards against endothelial dysfunction, inflammation and glucose-induced oxidative stress. It provides these cardioprotective properties by elevating production of calcium and nitric oxide, the latter through activation of the endothelial NO synthase signaling pathway. The obese, type 2 diabetics and those resistant to insulin show decreased levels of adinopectin. InLife Sciences, Grossini et al now show adiponectin treatment induces Porcine Aortic Endothelial Cells (PAOEC) to increase NO release and calcium movements during endothelial dysfunction like that caused by high-glucose. This signaling involves Akt, ERK1/2 and p38MAPK downstream AdipoR1. The results add new information about the control of endothelial function elicited by adiponectin in both physiological and pathological conditions. From these data, one can envision a beneficial role for adinopectin in endothelial function, and in preventing glucose-induced endothelial damage.

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Links:

http://press.endocrine.org/doi/pdf/10.1210/en.2016-1100

http://www.sciencedirect.com/science/article/pii/S0034528816302223

http://www.sciencedirect.com/science/article/pii/S0024320516304209