The Cell Biology of the Diseased Vessel Wall
The Vascular Biology Unit led by Dr. Richard Cohen seeks to understand mechanisms of vascular disease related metabolic dysfunction in order to better develop therapies. The role of reactive oxygen and nitrogen species is of key importance to that understanding. His group has found that in diabetes, hypertension, and atherosclerosis, the vasodilator, nitric oxide, reacts with superoxide anion, an oxidant produced in diseased blood vessels. As a result of this reaction even more potent oxidants, including peroxynitrite, are formed. Low levels of oxidants form protein cysteine thiol adducts with the low molecular weight antioxidant glutathione. Targeted proteins include the sarcoplasmic reticulum calcium ATPase, p21ras, and sirtuin-1, whose function is thereby altered, consequently modulating cell calcium and signaling in metabolic disease. Dr. Cohen is Co-PI of the Boston University NHLBI Cardiovascular Proteomics Center, in which his laboratory applies advanced proteomics methods to explore post-translational oxidative modifications of proteins in the cardiovascular system. His funded grants are studying the effect of diabetogenic high fat, high sucrose diet on aortic stiffness (RO1 HL105287), atherosclerosis (HL31607, PO1 HL068758), angiogenesis (R37 HL104017), and tissue and plasma proteomics (N01-HV-00239).
1.Tong X, Hou X, Jourd’heuil D, Weisbrod RM, Cohen RA. Upregulation of Nox4 by TGFb1 oxidizes SERCA and inhibits NO in arterial smooth muscle of the prediabetic Zucker rat. Circ Res. 2010;107(8):975-83. PubMed Central PMCID: PMC2955842.
2. Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E,
Shyy JY, Gao B, Wierzbicki M, Verbeuren TJ, Shaw RJ, Cohen RA, Zang M. AMPK
phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and
atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011;13(4):376-88. PMCID: PMC3086578.
3. Xu S, Jiang B, Hou X, Shi C, Bachschmid M, Zang M, Verbeuren TJ, Cohen RA. High Fat Diet Increases and the Polyphenol, S17834, Decreases Acetylation of the SirT1-Dependent Lysine-382 on p53 and Apoptotic Signaling in Atherosclerotic Lesion-Prone Aortic Endothelium of Normal Mice. J Cardiovasc Pharmacol. 2011 Sep;58(3):263-71. PMCID: PMC3168693.
4. Burgoyne JR, Haeussler DJ, Kumar V, Ji Y, Pimental DR, Zee RS, Costello CE, Lin C, McComb ME, Cohen RA, Bachschmid MM. Oxidation of HRas cysteine thiols by metabolic stress prevents palmitoylation in vivo and contributes to endothelial cell apoptosis. FASEB J. 2012;26(2):832-41. PMCID: PMC3290434
5. Qin F, Siwik DA, Luptak I, Hou X, Wang L, Higuchi A, Weisbrod RM, Ouchi N, Tu VH, Calamaras TD, Miller EJ, Verbeuren TJ, Walsh K, Cohen RA, Colucci WS. The polyphenols resveratrol and S17834 prevent the structural and functional sequelae of diet-induced metabolic heart disease in mice. Circulation. 2012; 125(14): 1757–1764. PMCID: PMC3354628
6. Li Y, Xu S, Jiang B, Cohen RA, Zang M. Activation of Sterol Regulatory Element
Binding Protein and NLRP3 Inflammasome in Atherosclerotic Lesion Development in Diabetic Pigs. PLoS One. 2013 Jun 25;8(6):e67532. PMCID: PMC3692453.