Cardiovascular & Lipid Disorders

David Askew

Yi-gang Wang, M.D., Ph.D

Pathology & Lab Med

Research Associate Professor

Research Summary

Over the past decade, I have pursued research in three related areas:

  1. Protection of the ischemic myocardium. We studied various cardioplegic solutions and measure hemodynamic changes to evaluate which solution provided greater protection against cardiac ischemic injury. Finally, we developed our own solution and used it clinical practice in Japan;
  2. Ischemic preconditioning against ischemia/reperfusion injury. We have studied the role of mitochondrial KATP channel opener, PKC, calcium, etc, on cardiac protection, its mechanisms and its signaling pathway;
  3. Stem cell therapy for treatment of myocardial infarction. Starting in 2001, I developed an interest in the use of stem cells to repair myocardial injury in collaboration with Dr. Ashraf.

Research interests are focused on stem cell therapy with three animal models including myocardial infarction (MI) via ligation of the left anterior descending (LAD) coronary artery, heterotopic heart transplantation and use of a temperature sensitive cell-sheet approach to treat MI. We are currently investigating an optimal such population of BMSC or expressing CXCR4 which possess great potential for migration, proliferation and ability to attenuate remodeling post infarction by releasing anti fibrotic enzymes. My laboratory also finds a synthetic bioactive peptide (SBP), which is highly angiogenic and mobilizes BMSCs form the bone marrow to the site of cardiac injury. Our preliminary data further revel that SBP induces proliferation of adult cardiomyocytes under in vitro and in vivo condition. We hope to develop a novel approach in promoting bone marrow derived stem cell based cardiac repair. The goal of my second NIH grant with a second project in my lab is to develop new strategies to treat the myocardial infarction through anti-fibrotic effects of CXCR4+-MSCs and use potential cell cycle reentry stimulants.

Selected Publications

Pasha Z, Wang Y, Sheikh R, Zhang D, Zhao T, Ashraf M. Preconditioning Enhances Cell Survival and Differentiation of Stem Cells during Transplantation in Infarcted Myocardium. Cardiovas Res. 2008;77:134-42.

Zhang D, Fan GC, Zhou X, Zhao T, Pasha Z, Xu M, Zhu Y, Ashraf M, Wang Y. Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium. JMCC. 2008;44(2):281-92.

Dai Y, Ashraf M, Zuo S, Uemura R, Dai YS, Wang Y, Haider HK, Li T, Xu M. Mobilized bone marrow progenitor cells serve as donors of cytoprotective genes for cardiac repair. J Mol Cell Cardiol. 2008; 44:607-17.

Prasad V, Bodi I, Meyer JW, Wang Y, Ashraf M, Engle SJ, Doetschman T, Sisco K, Nieman ML, Miller ML, Lorenz JN, Shull GE. Impaired cardiac contractility in mice lacking both the AE3 Cl-/HCO3- exchanger and the NKCC1 Na+-K+-2Cl- cotransporter: Effects on Ca2+ handling and protein phosphatases. J Biol Chem. 2008;283(46):31303-14.

Zhao T, Zhang D, Millard RW, Ashraf M, Wang Y. Stem cell homing and angiomyogenesis in transplanted hearts are enhanced by combined intramyocardial SDF-1α delivery and endogenous cytokine signaling. Am J Physiol Heart Circ Physiol. 2009 Jan 30. [Epub ahead of print].

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