Rosuvastatin attenuates the elevation in blood pressure induced by overexpression of human C-reactive protein

Departments of Internal Medicine, The Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Hypertension Research (Impact Factor: 2.66). 05/2011; 34(7):869-75. DOI: 10.1038/hr.2011.44
Source: PubMed


C-reactive protein (CRP) has been shown to function as an inflammatory factor to induce endothelial dysfunction and hypertension in rats. The anti-inflammatory effects of statins suggest that they may attenuate CRP-induced endothelial dysfunction and hypertension in Sprague-Dawley rats. Male Sprague-Dawley rats were injected with an adeno-associated virus (AAV) to induce overexpression of human CRP (AAV-hCRP) or green fluorescent protein (GFP) control (AAV-GFP). At 2 months after injection, rats were administered rosuvastatin by daily oral gavage (10 mg kg(-1)) for 2 additional months. Rosuvastatin administration attenuated the increased blood pressure and loss of vascular endothelial nitric oxide synthase expression in AAV-hCRP-treated rats, and N-nitro-L-arginine methyl ester blocked its hypotensive effect. Rosuvastatin also activated phosphoinositide 3-kinases/Akt, and inhibited Rho kinase activity in aorta. Rosuvastatin reduced the production of reactive oxygen species through downregulation of nicotinamide adenine dinucleotide phosphate oxidase subunits, p22 phox and gp91 phox, and upregulation of superoxide dismutase 1 expression. Rosuvastatin attenuated the increase in blood pressure in AAV-hCRP-treated rats through endothelial protection and antioxidant effects. Our data reveals a novel mechanism through which statins may lower blood pressure.

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    • "Proteins were detected by immunoblotting and visualized using enhanced chemiluminescence. Procedures were performed as described previously [22]. "
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    ABSTRACT: 20-hydroxyeicosatetraenoic acid (20-HETE) induces endothelial dysfunction and is correlated with diabetes. This study was designed to investigate the effects of 20-HETE on endothelial insulin signaling.Human umbilical vein endothelial cells (HUVECs) or C57BL/6J mice were treated with 20-HETE in the presence or absence of insulin, and p-ERK1/2, p-JNK, IRS-1/PI3K/AKT/eNOS pathway, were examined in endothelial cells and aortas by immunoblotting. eNOS activity and nitric oxide production were measured. 20-HETE increased ERK1/2 phosphorylation and IRS-1 phosphorylation at Ser616; these effects were reversed by ERK1/2 inhibition. We further observed that 20-HETE treatment resulted in impaired insulin-stimulated IRS-1 phosphorylation at Tyr632 and subsequent PI3-kinase/Akt activation. Furthermore, 20-HETE treatment blocked insulin-stimulated phosphorylation of eNOS at the stimulatory Ser1177 site, eNOS activation and NO production; these effects were reversed by inhibiting ERK1/2. Treatment of C57BL/6J mice with 20-HETE resulted in ERK1/2 activation and impaired insulin-dependent activation of the IRS-1/PI3K/Akt/eNOS pathway in the aorta. Our data suggest that the 20-HETE activation of IRS-1 phosphorylation at Ser616 is dependent on ERK1/2 and leads to impaired insulin-stimulated vasodilator effects that are mediated by the IRS-1/PI3K/AKT/eNOS pathway.
    PLoS ONE 04/2014; 9(4):e95841. DOI:10.1371/journal.pone.0095841 · 3.23 Impact Factor
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    • "These effects are considered to be mediated by the beneficial effects of statins on endothelial function, their interactions with the renin–angiotensin system, and their influence on large artery compliance.36,37 Some animal studies showed that rosuvastatin reduced blood pressure in spontaneously hypertensive rats and in rats with C-reactive protein (CRP)-induced endothelial dysfunction and hypertension, and these effects appeared to be related to its endothelial protection and antioxidant effects.41,42 Future randomized controlled trials are needed to investigate the blood pressure-lowering effect of rosuvastatin in patients with increased cardiovascular risk. "
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    Integrated Blood Pressure Control 04/2013; 6:15-25. DOI:10.2147/IBPC.S34814
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    • "However, the effects are consistent with previous findings insofar that insulin at supraphysiological concentrations increases [3H]thymidine incorporation in endothelial cells [33]. Insulin and rosuvastatin have also been shown to activate the PI3K/Akt pathway, a pathway that is well known to be involved in cell survival and proliferation [18,22,34-36]. BLX-1002 is a novel compound of the TZD family, but with no apparent PPAR affinity. "
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