Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00546 (Rosuvastatin)
 453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, also known as statins, have been shown to reduce cardiac remodeling. Angiotensin II (Ang II) type 1 receptor (AT1R) and oxidized low-density lipoprotein (ox-LDL) via its lectin-like ox-LDL receptor (LOX-1) are major stimuli for cardiomyocyte growth. We postulated that rosuvastatin, a potent HMG-CoA reductase inhibitor, may reduce Ang II-mediated cardiomyocyte growth via AT1R and LOX-1 inhibition. HL-1 adult mouse cardiomyocytes were incubated overnight in serum-free medium, and then treated with rosuvastatin, the AT1R inhibitor losartan or anti-LOX-1 antibody for 3 hours. The cells were then stimulated with Ang II. We measured cardiomyocyte growth, and associated intracellular redox signals using reverse transcription- polymerase chain reaction (RT-PCR) and real-time quantitative PCR. Losartan and anti-LOX-1 antibody markedly attenuated Ang II-mediated oxidant stress, and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p40(phox) and gp91(phox) subunits) and nuclear factor-kappaB (NF-kappaB). Rosuvastatin attenuated the Ang II-mediated upregulation of both subunits of NAPDH oxidase as well as NF-kappaB. Rosuvastatin also reduced Ang II-mediated upregulation of AT1R and LOX-1. In other experiments, LOX-1 was upregulated in cardiomyocytes by transfection with pCI-neo/LOX-1, which also enhanced the expression AT1R messenger RNA (mRNA), and rosuvastatin pretreatment reduced the expression of both LOX-1 and AT1R in this system. Thus, rosuvastatin attenuates Ang II-mediated cardiomyocyte growth by inhibiting LOX-1 and AT1R expression and suppressing the heightened intracellular redox state.
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PMID:Rosuvastatin attenuates Ang II--mediated cardiomyocyte hypertrophy via inhibition of LOX-1. 1972 24

Rosuvastatin is a promising synthetic hydrophillic statin which provides potential benefits in reducing cardiovascular risk factors. Rosuvastatin has potent ability to diminish low density lipoprotein, very low density lipoprotein, triglycerides and enhance high density lipoprotein level to manage high cholesterol level and associated cardiovascular diseases. Intriguingly, numerous studies demonstrated that rosuvastatin can reverse the cardiac disorders such as hypertension, atherosclerosis, ischemic heart disease, congestive heart failure and cardiomyopathy by reducing reactive oxygen species mediated oxidative stress. Rosuvastatin maintain the balance between oxidant generation and oxidant scavenging by reducing NADPH (nicotinamide adenine dinucleotide phosphate)-dependent production of reactive oxygen species, suppressing endothelial nitric oxide synthase (eNOS) uncoupling, inducing and upregulating antioxidant defense mechanism. This review, summaries pleiotropic antioxidant evidences of rosuvastatin in favor of cardioprotection.
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PMID:Pleiotropic antioxidant potential of rosuvastatin in preventing cardiovascular disorders. 2364 61