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)

Among the numerous risk factors for atherosclerosis, 2 are particularly important: hypertension and primary or secondary abnormalities of plasma lipids and lipoproteins. Antihypertensive treatments significantly decrease the risk of cerebrovascular accidents, renal failure or hypertensive cardiomyopathy, but they have little influence on coronary artery disease. It has been suggested that some antihypertensive agents may have deleterious effects by altering serum lipoproteins and this may override the benefit of blood pressure reduction. Diuretics increase the blood concentration of total cholesterol, low-density lipoproteins and triglycerides. Indapamide, a methylindoline agent with vasodilator activity, has no adverse lipid effects. Twenty-six studies have clearly demonstrated that indapamide appears to be unique among diuretics because of an absence of adverse lipid effects. In some studies indapamide significantly increased high-density lipoprotein cholesterol, apoproteins A1, A2 and apoprotein E. When a thiazide diuretic had been given previously, indapamide treatment normalized the lipid and lipoprotein profiles. The reason for the lack of adverse lipid effects of indapamide is discussed. Thus indapamide, 2.5 mg once daily, is effective and safe for the control of mild to moderate hypertension, both in young and older patients. It may be an optimal diuretic for use in normolipidemic or hyperlipidemic patients, as it increases high-density lipoprotein but not low-density lipoprotein cholesterol.
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PMID:Beneficial effects of indapamide on lipoproteins and apoproteins in ambulatory hypertensive patients. 218 57

Diabetes is a risk factor for coronary atherosclerosis, myocardial infarction, and ischemic cardiomyopathy. Insulin resistance is associated with left ventricular (LV) hypertrophy and hypertensive cardiomyopathy. Even in the absence of coronary artery disease or hypertension, "diabetic cardiomyopathy" can develop because of myocardial autonomic dysfunction or impaired coronary flow reserve. The relationship between insulin resistance and cardiomyopathy is bidirectional. Systemic and myocardial glucose uptake is compromised in heart failure independent of etiology. These abnormalities are associated with cellular deficits of insulin signaling. Insulin resistance in heart failure can be detrimental, because transcriptional shifts in metabolic gene expression favor glucose over fat as a substrate for high-energy phosphate production. Although preexisting diabetes accelerates this process of "metabolic death," insulin resistance can also develop secondary to cardiomyopathy-associated overabundance of neurohormones and cytokines. Insulin resistance and fatty acid excess are potential therapeutic targets in heart failure, striving for efficient myocardial substrate utilization. Peroxisome proliferator activator receptor gamma (PPARgamma) agonists are antidiabetic agents with antilipemic and insulin-sensitizing activity. Experimental studies suggest salutary effects in limiting infarct size, attenuating myocardial reperfusion injury, inhibiting hypertrophic signaling and vascular antiinflammatory actions through cytokine inhibition. However, clinical applicability in diabetic patients experiencing heart failure has been hampered because of increased edema and even fewer reports of exacerbation associated with these compounds. Evidence to date argues for peripheral mechanisms of edema unrelated to central hemodynamics. Nevertheless, they are currently contraindicated in New York Heart Association (NYHA) III-IV patients, particularly in combination with insulin. Investigations are underway to decipher mechanisms, risks, and benefits of PPARgamma agonists, as well as the role of the structurally related PPARalpha receptor on cardiovascular metabolism and function.
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PMID:Peroxisome proliferator activator receptors (PPAR), insulin resistance, and cardiomyopathy: friends or foes for the diabetic patient with heart failure? 1507 85

RhoA and Rho-kinase (ROCK) participate in a wide variety of cell signal functions such as cell growth, smooth and cardiac muscle contraction, cytoskeleton rearrangement, cell migration and proliferation. In vascular smooth muscle cells, RhoA and ROCK play an important role in Ca2+ sensitization and regulate vascular smooth muscle tone. In the heart, RhoA and ROCK mediate hypertrophic response leading to cardiac hypertrophy. Recent cellular and molecular biology studies using ROCK inhibitors such as Y-27632 and fasudil have indicated a pivotal role of the RhoA-ROCK cascade in many aspects of cardiovascular function such as cardiac hypertrophy and ventricular remodeling following myocardial infarction. Inhibition of the RhoA-ROCK signaling pathway may be a suitable target for a number of cardiovascular diseases including hypertension, atherosclerosis, diabetes and hypertrophic heart failure. This review focuses on the current understanding of the RhoA-ROCK signal pathway in heart diseases and discusses the use of ROCK inhibitors as therapeutic agents for heart diseases ranging from hypertensive cardiomyopathy to heart failure.
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PMID:Small guanine nucleotide-binding protein Rho and myocardial function. 1571 22