The Experts below are selected from a list of 30177 Experts worldwide ranked by ideXlab platform
Luis M Moura - One of the best experts on this subject based on the ideXlab platform.
-
the Lipid Hypothesis in calcific aortic valve disease the role of the multi ethnic study of atherosclerosis
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Nalini M Rajamannan, Luis M MouraAbstract:Calcific aortic valve disease (CAVD) is the most common indication for valve intervention in the world.1 The cellular mechanisms, cardiovascular risk factors, and therapeutic interventions have been under intense investigation in the 21st century. In the study published in ATVB , Cao et al2 tested the Multi-Ethnic Study of Atherosclerosis (MESA) database to define the calcification phenotype associated with unique lipoprotein mechanisms in the development of calcification. MESA was designed to test subclinical atherosclerosis markers and measure calcification burden in the aortic valve using computed tomography measurements. The study group included individuals from age 45 to 84 years, who were free of any clinical cardiovascular disease and treated diabetes mellitus.3,4 The database is robust to test for subclinical risk factors in the development of calcific aortic valve disease. See accompanying article on page 1003 O’Brien et al5 and Otto et al6 publish studies to define the role of lipoproteins in ex vivo calcified aortic valves. Over the next 20 years, studies in the field of calcific aortic valve disease have determined that the calcific aortic valve disease is not a degenerative process, but an active cellular biology. …
Marc R Dweck - One of the best experts on this subject based on the ideXlab platform.
-
quest for pharmacotherapy in aortic valve stenosis the Lipid Hypothesis
Heart, 2020Co-Authors: Kang H Zheng, Marc R DweckAbstract:Aortic stenosis was first described by the French surgeon and anatomist Lazare Riviere in 1663. While the last decade has seen impressive advances in our ability to treat aortic valve stenosis invasively and percutaneously, significant issues remain with regards to the optimal timing of valve replacement, periprocedural risks and long-term durability. There therefore remains major interest in developing medical treatments to halt or slow progression of aortic stenosis, which could obviate the need for surgical intervention altogether. A stitch in time saves nine; however, no pharmacotherapies are currently proven to be effective for the treatment of calcific aortic valve stenosis (CAVS). Atherogenic apolipoprotein B-containing lipoproteins, such as low-density lipoprotein (LDL) and lipoprotein(a) (Lp(a)), have clearly been implicated in the pathogenesis of aortic stenosis, particularly in the early initiation phase. However, LDL cholesterol lowering with statins or ezetimibe failed to modify progression of aortic valve stenosis in multiple randomised clinical trials (SEAS, SALTIRE and ASTRONOMER). Attention has instead switched to Lp(a), with a growing body of epidemiology, genetics and prospective imaging studies having built a convincing case for elevated Lp(a) levels being associated with an increased incidence of aortic stenosis, …
Linda L Demer - One of the best experts on this subject based on the ideXlab platform.
-
atherogenic diet and minimally oxidized low density lipoprotein inhibit osteogenic and promote adipogenic differentiation of marrow stromal cells
Journal of Bone and Mineral Research, 1999Co-Authors: Farhad Parhami, Mary C Territo, Simon Mark Jackson, Yin Tintut, Jennifer P Balucan, Linda L DemerAbstract:In osteoporosis, the bone marrow stroma osteogenic cell population declines and adipocyte numbers increase. We recently showed that oxidized Lipids inhibit differentiation of preosteoblasts. In this report, we assess the effect of minimally oxidized low density lipoprotein (MM-LDL) on osteoblastic differentiation of murine marrow stromal cells, M2–10B4. MM-LDL, but not native LDL, inhibited stromal cell osteoblastic differentiation as demonstrated by inhibition of alkaline phosphatase activity, collagen I processing, and mineralization, through a mitogen-activated protein kinase–dependent pathway. In addition, marrow stromal cells from C57BL/6 mice fed a high fat, atherogenic diet failed to undergo osteogenic differentiation in vitro. The ability of MM-LDL to regulate adipogenesis was also assessed. Treatment of M2–10B4 as well as 3T3-L1 preadipocytes with MM-LDL, but not native LDL, promoted adipogenic differentiation in the presence of peroxisome proliferator-activated receptor (PPAR) γ agonist thiazolidinediones, BRL49653 and ciglitizone. Based on promoter-reporter construct experiments, MM-LDL may be acting in part through activating PPARα. These observations suggest that LDL oxidation products promote osteoporotic loss of bone by directing progenitor marrow stromal cells to undergo adipogenic instead of osteogenic differentiation. These data lend support to the “Lipid Hypothesis of osteoporosis.”
-
Lipid Hypothesis of cardiovascular calcification
Circulation, 1997Co-Authors: Linda L DemerAbstract:Prosthetic heart valve calcification can be a devastating event, especially in young children. In this issue of Circulation, Vyavahare et al1 make the important observation that bioprosthetic heart valve calcification is prevented by valvular pretreatment with ethanol. Not only do these findings have a direct impact on treatment of patients with valvular heart disease, they also provide clues about the fundamental mechanisms underlying calcification of bioprosthetic valves as well as native valve disease and atherosclerotic plaque in general. A particularly important question raised by this study is whether Lipids and/or protein modification is an etiologic factor in cardiovascular calcification. To explain the negative effects of ethanol on bioprosthetic calcification, Vyavahare and colleagues1 identified three possible mechanisms: elimination of phosphoLipids and cholesterol, changes in collagen fiber conformation, and possible direct effects of ethanol on osteocalcin and/or the calcification process. Although they provide evidence for the first two possibilities, the following analysis suggests that the first mechanism predominates. ### Lipid Extraction Although ethanol treatment extracted almost all the Lipid elements, the authors did not consider this the sole mechanism because the alternative method of Lipid extraction, chloroform-methanol treatment, had less effect on calcification than ethanol despite an even more effective extraction. However, technical factors may need to be considered further because other investigators2 3 4 using chloroform-methanol extraction in a similar …
Nalini M Rajamannan - One of the best experts on this subject based on the ideXlab platform.
-
the Lipid Hypothesis in calcific aortic valve disease the role of the multi ethnic study of atherosclerosis
Arteriosclerosis Thrombosis and Vascular Biology, 2016Co-Authors: Nalini M Rajamannan, Luis M MouraAbstract:Calcific aortic valve disease (CAVD) is the most common indication for valve intervention in the world.1 The cellular mechanisms, cardiovascular risk factors, and therapeutic interventions have been under intense investigation in the 21st century. In the study published in ATVB , Cao et al2 tested the Multi-Ethnic Study of Atherosclerosis (MESA) database to define the calcification phenotype associated with unique lipoprotein mechanisms in the development of calcification. MESA was designed to test subclinical atherosclerosis markers and measure calcification burden in the aortic valve using computed tomography measurements. The study group included individuals from age 45 to 84 years, who were free of any clinical cardiovascular disease and treated diabetes mellitus.3,4 The database is robust to test for subclinical risk factors in the development of calcific aortic valve disease. See accompanying article on page 1003 O’Brien et al5 and Otto et al6 publish studies to define the role of lipoproteins in ex vivo calcified aortic valves. Over the next 20 years, studies in the field of calcific aortic valve disease have determined that the calcific aortic valve disease is not a degenerative process, but an active cellular biology. …
Daniel Steinberg - One of the best experts on this subject based on the ideXlab platform.
-
in celebration of the 100th anniversary of the Lipid Hypothesis of atherosclerosis
Journal of Lipid Research, 2013Co-Authors: Daniel SteinbergAbstract:This year marks the 100th anniversary of the publication of Anitschkow's classic paper proposing the central role of hypercholesterolemia in atherogenesis. We at the Journal of Lipid Research take this occasion to acknowledge the debt we all owe to Anitschkow and his colleagues for getting us on the right track. As discussed below in detail, his contributions were insightful and went well beyond simply pinpointing hypercholesterolemia as a major etiologic factor. Anitschkow's work led him to define most of the key elements in the initiation and evolution of lesions in animal models of atherogenesis.
-
thematic review series the pathogenesis of atherosclerosis an interpretive history of the cholesterol controversy part v the discovery of the statins and the end of the controversy
Journal of Lipid Research, 2006Co-Authors: Daniel SteinbergAbstract:The first four reviews in this series (Steinberg, D. 2004. J. Lipid Res. 45: 1583-1593; Steinberg, D. 2005. J. Lipid Res. 46: 179-190; Steinberg, D. 2005. J. Lipid Res. 46: 2037-2051; Steinberg, D. 2006. J. Lipid Res. 47: 1-14) traced the gradual accumulation of evidence, evidence of several different kinds, supporting the Lipid Hypothesis. They tracked the history from Anitschkow's 1913 classic work on the cholesterol-fed rabbit model to the breakthrough 1984 Coronary Primary Prevention Trial, the first large, randomized, double-blind primary intervention trial showing that decreasing blood cholesterol (using cholestyramine) significantly reduces coronary heart disease events. At that point, for the first time, decreasing blood cholesterol levels became an official national public health goal. Still, only a small fraction of patients at high risk were getting appropriate cholesterol-lowering treatment, and a number of important clinical questions remained unanswered. This final review in the series traces the early studies that led to the discovery of the statins and briefly reviews the now familiar large-scale clinical trials demonstrating their safety and their remarkable effectiveness in reducing coronary heart disease morbidity and mortality.