Day 1 :
University of Central Florida, USA
Time : 10:10-10:40
Sampath Parthasarathy was instrumental in the development of the concept of oxidized LDL and its contribution to atherosclerosis, a major form of cardiovascular disease. He is currently at University of Central Florida as the Florida Hospital Chair in Cardiovascular Sciences and the Associate Dean of Research. Dr. Parthasarathy has published over 250 articles and has served on numerous editorial boards and NIH committees. He has been continuously funded by NIH and other agencies for over 30 years and he was awarded the distinguished service Award by the American Heart Association and by the American Association of Cardiologists of Indian Origin and from SASAT International. He is also the recipient of the prestigious van Deenen Memorial award for lipids and the Ranbaxy Award for excellence in cardiovascular research.
Background: Cardiovascular diseases, including atherosclerosis, are the leading cause of death in the United States. Atherosclerotic lesions are formed by deposition of lipids in the intima of arteries. Upon exposure to oxidative stresses, low-density lipoprotein (LDL) is converted to highly atherogenic oxidized LDL (ox-LDL) particles, which contribute to disease development and progression. Advanced disease stages may result in calcification of lesions. This calcification process is important, as it has been shown to be associated with stable plaques that are less prone to rupture. Calcification is present in lipid rich domains of lesions and correlates well with overall plaque burden. However, neither the composition of the mineralized calcium deposits nor its relationship to lipid peroxidation is known.rnMethods: In this study, the potential of lipid peroxide-derived lipophilic dicarboxylic acid (DCA, e.g. azelaic acid) to promote calcification upon exposure to vascular smooth muscle cells was tested. Using 13-Hydroperoxyoctadecadienoic acid (13-hydroperoxylinoleic acid, 13-HPODE) and thin-layer and gas chromatography–mass spectrometry we characterized the conditions where HPODE is decomposed to aldehyde product 9-oxo-nonanoic acid and its corresponding DCA azelaic acid (AZA).rnResults: HPODE treatment resulted in the cellular conversion to ONA and AZA as determined by GC-MS. Both free AZA and intracellular delivery of AZA via lyso phosphatidylcholine (lysoPtdCho) micelles induced calcification of aortic smooth muscle cells, as determined by Von Kossa and alizarin red staining. rnConclusion: These results demonstrate that DCAs may contribute to atherosclerotic calcification thus accounting for the latter’s relationship to plaque burden and association with lipids. This study also challenges the dogma that arterial calcification represents the deposition of calcium phosphate. Our future work aims to delineate the association of calcium with lipid rich plaques and lipid oxidation with calcification in animal and human atherosclerosis.rn
University of Texas McGovern School of Medicine USA
Time : 10:00-10:30
In 1982 Dr. Yong-Jian Geng graduated from Suzhou Medical College, China. In 1994, he obtained doctoral degree of medical science from Goethenburg University, and then pursued his cardiology fellowship, and in 1995, was appointed as instructor of medicine at Harvard Medical School. In 1999, Dr. Geng joined the faculty of Schoo of Medicine, University of Texas Health Science Center at Houston. In 2000 he was appointed Director of the Center for Cardiovascular Biology and Atherosclerosis Research, and in 2001, he was named Director of Stem Cells and Heart Failure Research at Texas Heart Institute. Dr. Geng was promoted to Professor of Medicine in 2005.
Cellular accumulation, lipid deposition and connective tissue formation in the arterial intima characterizes the development of atherosclerotic plaques. However, the increased cell mass in the intima does not reflect the rates of cell growth and death. Over the long-lasting process of atherogenesis often for several decades, many plaque cells may undergo apoptosis, a form of programmed cell death. Atherosclerosis and hypertension are closely associated chronic arterial diseases. In many case, they co-exist and interplay, triggering the development of life-threatening complications, such as myocardial and cerebral infarctions. Increased apoptosis and phenotypic alteration of vascular cells occur in the arterial wall with various pathological conditions, including atherosclerosis and hypertension. Several molecular pathways contribute to the changes of cellular components in atherosclerotic lesions. Maintaining normal structure and shape of the blood vessels requires a balance between apoptosis and proliferation. During the pathogenesis of atherosclerosis and hypertension, vascular cells may become malfunctional or injured by various potentially harmful factors. Vascular smooth muscle cells exposed to pro-atherogenic and hypertensive factors are undergoing phenotypic changes, which transform the cells from contractile to synthetic styles. Two prominent pathological alterations are reduction of vascular cell survival and promotion of calcification. Those processes are regulated by an epigenetic process involved in expression of different epigenetic factors. Clarification of these pathways may aid development of novel therapeutic strategies to treat atherosclerotic hypertension, and its complications, including the acute coronary syndromes. The attenuation of apoptosis and calcifification increases the cellularity and reduces stiffness and vulnerability for rupture in the arterial wall.