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Control

HHcy

HHcy + Hcy-lowering

HOW DOES HYPERHOMOCYSTEINEMIA TRIGGER ENDOTHELIAL DYSFUNCTION? A Risk Factor that Rivals Smoking and Hyperlipidemia Hong Wang, MD, PhD, and her Temple group are national leaders in the search for a cure for hyperhomocysteinemia (HHcy), an amino acid metabolic disorder that is a potent independent risk factor for cardiovascular disease. Dr. Wang’s team discovered a unique biochemical mechanism by which HHcy causes DNA methylation suppression selectively in endothelial cells—an action that delays post-injury endothelial repair and contributes to vascular remodeling and spontaneous atherosclerosis. Dr. Wang’s laboratory also described a mechanism by which HHcy causes potassium channel dysfunction and impaired endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation of resistance arterioles. They have made the case that inhibition of small- or intermediate conductance Ca2+ may trigger the EDHF-mediated responses that presage at herothrombic disease. Recently, they reported that HHcy causes systemic and vessel wall inflammation via promoter inflammatory monocyte subset differentiation.

ABOVE Atherosclerotic fatty plaque

thickening (bright red) in the aortas of hyperhomocysteinemia (HHcy) mice is effectively reversed using Hcy-lowering vitamin therapy (HHcy+).

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HEART | LUNG

Ongoing studies with a novel array of models (e.g., metabolic, epigenetic, transgenic mouse) and advanced molecular techniques are aimed at verifying the exact risk triggers of HHcy—and then blocking them to elicit protective vascular effects. Impaired insulin receptor signaling is also being probed in HHcy and other high-risk vascular states.

Profile for Temple Health

Temple University School of Medicine - Highlights of Basic and Clinical Research - 2014  

Temple University School of Medicine is pushing the boundaries of science to help reduce the devastating effects of heart and lung disease,...

Temple University School of Medicine - Highlights of Basic and Clinical Research - 2014  

Temple University School of Medicine is pushing the boundaries of science to help reduce the devastating effects of heart and lung disease,...