Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Available information regarding the relation among atherosclerosis, low-density lipoproteins, markers of thrombosis, inflammation and endothelial dysfunction has accumulated, but is still very limited, making only minimal contributions to clinical decision-making. Many more clinical trials are needed, but unless there is a relationship between atherosclerosis prevention, specific markers and a pharmaceutical product, financial support for such trials will be difficult to obtain. The anti-inflammatory effect of statins is well established. Angiotensin-converting enzyme inhibitors are generally not thought of as having anti-inflammatory effects, but the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) study observed extensive RR reduction with perindopril. It was explained not simply by control of hypertension, but by reduced activity of multiple factors, supported by specific substudies. The 'cardiovascular continuum' is an excellent unifying term to explain atherosclerosis mechanisms, relate mechanisms to clinical understanding, and assist the clinician in selecting the appropriate prevention and control therapies. This so-called continuum actually describes a relationship among different biochemical, enzymatic and hormonal factors that affect the cardiovascular system. It can be seen in the downregulation of the angiotensin II receptor type 1 by statins, which contributes to hypertension control while lowering low-density lipoproteins. Peroxisome proliferator activator receptor-gamma also demonstrates the cardiovascular continuum with activation of the receptor by glitazones. The glitazones increase insulin sensitivity for diabetes control. Activation of the peroxisome proliferator activator receptor-gamma inhibits inflammation, which is possibly related to atherosclerosis, normalization of endothelial function, suppression of metalloproteinases and a decrease in smooth muscle cell migration. All of these effects may decrease atherosclerosis production while improving control of diabetes mellitus, a key disease in the cardiovascular continuum for development of atherosclerosis. Consideration of such interrelationships is just scratching the surface. Nevertheless, it can be seen that the complicated process of atherosclerosis development has a multifaceted explanation that has been minimally defined, but holds the key to prevention and control of this major medical problem faced in modern society.
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PMID:Coronary atherosclerosis, low-density lipoproteins and markers of thrombosis, inflammation and endothelial dysfunction. 2247 42

Cardiovascular disease, despite all the recent advances in treatment of the various risk factors, remains the major cause of mortality in both type 1 and type 2 diabetes. Experimental models of diabetes-associated atherosclerosis, despite their limitations in recapitulating the human context, have assisted in the elucidation of molecular and cellular pathways implicated in the development and progression of macrovascular injury in diabetes. Our own studies have emphasized the role of oxidative stress and advanced glycation and identified potential targets for vasoprotective therapies in the setting of diabetes. Furthermore, it has been clearly shown that previous episodes of hyperglycemia play a key role in promoting end-organ injury in diabetes, as shown in clinical trials such as the UK Prospective Diabetes Study (UKPDS), Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Observational Study (ADVANCE-ON), and the Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC). The cause of this phenomenon, known as metabolic memory, remains to be elucidated, but it appears that epigenetic pathways, including glucose-induced histone methylation, play a central role. Further delineation of these pathways and their link to not only glucose but also other factors implicated in vascular injury should lead to more rational, potentially more effective therapies to retard diabetes-associated cardiovascular disease.
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PMID:Metabolic Karma-The Atherogenic Legacy of Diabetes: The 2017 Edwin Bierman Award Lecture. 2967 24


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