Imaging the Vascular Consequences of Lipid Deposition

Boston University Medical Campus, Boston MA

Investigators

Linked publications & trials

Abstract

Patients with metabolic syndrome, who are invariably obese, exhibit a cluster of risk factors for[unreadable] cardiovascular disease including diabetes mellitus, hypertension, and abnormalities in cholesterol[unreadable] metabolism. The major morbidity in such patients is myocardial infarction and stroke caused by accelerated[unreadable] atherosclerosis. The complex pathophysiological disturbances that promote atherogenesis also include[unreadable] chronic inflammation, adipocyte endocrine dysfunction, and abnormalities in vascular compliance. The[unreadable] development of insulin resistance is a critical underlying feature of metabolic syndrome, which results in[unreadable] abnormal levels of insulin and other hormones. We hypothesize that in addition to the enhanced deposition[unreadable] of lipid in large, well-characterized subcutaneous and visceral fat stores, another unifying feature of[unreadable] metabolic syndrome is innapropriate deposition of lipid in smaller depots. These inappropriate stores include[unreadable] hepatocellular triglyceride, perivascular and pericardial triglyceride, and atherosclerotic cholesterol, which[unreadable] may serve as localized markers of disease. We further hypothesize that decection of these lipid stores noninvasively[unreadable] in a site-specific manner will provide new insights into mechanisms by which they exert systemic[unreadable] effects and illuminate specific risk factors for determining adverse outcomes. Magnetic resonance imaging[unreadable] (MRI) is a non-invasive tool that can detect the pathological lipid deposition and identify early atherosclerotic[unreadable] vascular changes. We will use MR-based techniques to identify site-specific abnormalities in obese patients[unreadable] with metabolic syndrome but without known atherosclerosis who are undergoing medically supervised weight[unreadable] loss and/or gastric bypass (bariatric) surgery. We will apply MRI to identify changes in vascular stiffness and[unreadable] correlate these changes to the concentration of lipid in the vessel (atherosclerotic plaque) and surrounding[unreadable] the blood vessel (triglyceride). We will quantify triglyceride stores in the liver and surrounding the heart and[unreadable] blood vessels (perivascular/pericardial fat), and associate these findings with hormone levels and the[unreadable] presence of early atherosclerotic disease. We will monitor regression of these parameters in patients with[unreadable] metabolic sydnrome following successful weight loss. In patients with metabolic syndrome but advanced[unreadable] atherosclerosis who are undergoing carotid endarterectomy, we will use molecular MR techniques to[unreadable] determine evidence of inflammation and plaque vulnerability and perform in vivo and ex vivo studies to[unreadable] quantify lipid. This work will elucidate the complex interplay between risk factors and clinical phenotype,[unreadable] through the demonstration of which lipid deposits are most detrimental to future health. An important[unreadable] outcome our work will be a non-invasive MR-based protocol that will further stratify cardiovascular risk in this[unreadable] increasingly prevalent cohort of patients, and provide a means to evaluate the efficacy of specific therapies.