Aksam J. Merched, Ph.D.
Department of Molecular and Cellular Biology
Ph.D.: University of Nancy, Nancy, France
Postdoctoral training: Baylor College of Medicine, Houston
Hypercholesterolemia, Inflammation and Autoimmunity in Atherosclerosis and Cardiovascular Diseases
Cardiovascular disease is the leading cause of death in Western society. Atherosclerosis, or hardening of the arteries, underlies heart attacks and stroke, which accounts for the majority of cardiovascular deaths. Atherosclerosis results from chronic inflammation of the artery wall. Our latest research on the inflammatory basis of atherosclerosis led to the identification of some chemical mediators that are responsible for terminating the inflammatory insult and the return to homeostasis in the vessel wall. Some of these pro-resolution mediators are derived from omega-3 polyunsaturated fatty acids (PUFAs), highly present in certain types of fish. We also found that deficiency in the body’s ability to produce these mediators is behind the failed resolution that results in unabated inflammation and progression of atherosclerosis. Our findings provide the first evidence that resolution of vascular inflammation via specific chemical mediators of resolution plays a key role in keeping atherosclerosis at bay. Exploitation of this new concept may lead to the development of new anti-atherosclerosis drugs.
More recently, we are investigating the role of autoimmunity in vascular inflammation and atherosclerosis using some unique mouse models and applying the proteomic approach to uncover the cellular basis of autoimmunity and its molecular targets in the arteries.
Aggressive build up of lesions in aorta of murine model of atherosclerosis
Baylor College of Medicine
One Baylor Plaza, Alkek N520.11
Houston, TX 77030
- Merched AJ, Ko K, Gotlinger K, Serhan CN and Chan L. (2008). Atherosclerosis: Evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB Journal (in press).
- Cheng J, Zhang J, Merched A, Zhang L, Zhang P, Truong L, Boriek AM and Du J. (2007). Mechanical stretch suppresses Ox-LDL-induced apoptosis in vascular smooth muscle cells by upregulating integrin alpha vbeta 3 and stabilization of PINCH-1. J Biol Chem 282(47):34268-75.
- Lau PP, Li L, Merched AJ, Zhang AL, Ko KWS and Chan L. (2006). Nicotine Induces Proinflammatory Responses in Macrophages and the Aorta Leading to Acceleration of Atherosclerosis in LDLR-/- Mice. Arteriosclerosis Thrombosis and Vascular Biology 26(1):143-9.
- Merched A and Chan L. (2004). Absence of p21Waf1/Cip1/Sdi1 alters macrophage differentiation and inflammatory response and protects against atherosclerosis. Circulation 110(25):3830-41. Followed by Editorial: Andrés V, pp 3749-3752.
- Nomura S, Merched A, Nour E, Dieker C, Oka K and Chan L. (2004). LDL Receptor gene therapy with helper-dependent adenovirus produces long-term protection in a mouse model of familial hypercholesterolemia. Gene Therapy 11(20):1540-8.
- Serhan CN, Jain A, Marleau S, Clish C, Kantarci A, Behbehani B, Colgan SP, Stahl GL, Merched A, Petasis NA, Chan L and Van Dyke TE. (2004). Reduced inflammation and tissue damage in transgenic rabbits overexpressiong 15-lipoxygenase and endogenous anti-inflammatory lipid mediators. Journal of Immunology 171(12):6856-65.
- Merched A, Williams E and Chan L. (2003). Macrophage-specific p53 expression plays a crucial role in atherosclerosis development and plaque remodeling. Arteriosclerosis Thrombosis and Vascular Biology 23(9):1608-14.
- Belalcazar M *, Merched A*, Carr B, Antanova E, Chen K-H, Oka K, Lucio P, Beaudet A and Chan L. (2003). Long-term stable expression of human apolipoprotein A-I mediated by helper-dependent adenovirus gene transfer inhibits atherosclerosis progression and remodels atherosclerotic plaques in a mouse model of familial hypercholesterolemia. Circulation 107(21):2726-32. * Equal contribution.
- Oka K, Pastore L, Kim I-H, Merched A, Nomura S, Lee H-J, Merched-Sauvage M, Arden-Riley C, Lee B, Finegold M, Beaudet A and Chan L. (2001). Long-term reversal of hypercholesterolemia and prevention of atherosclerosis development in LDL receptor-deficient mice by transfer of the VLDL receptor gene in vivo using helper-dependent adenoviral vector. Circulation 103(9):1274-81.
- Merched A, Xia Y, Visvikis S, Serot JM and Siest G. (2000). Decreases in high density lipoprotein- cholesterol and serum apolipoprotein AI concentrations are highly correlated with the severity of Alzheimer's disease. Neurobiology of Aging 21(1):27-30.