CRP induces hypertension in animal models: homo sapiens says NO

Abstract

C -reactive protein (CRP) is a prototypic downstream marker of inflammation.Recent data have suggested that CRP is an independent risk marker for cardiovascular disease. In addition, numerous lines of evidence support the thesis that CRP could participate in atherothrombosis. 1 In both in-vitro and in-vivo studies, one of the most uniform findings is the inhibition of endothelial nitric oxide synthase (eNOS) and impaired endothelial vasoreactivity, following CRP administration. 2 Epidemiological studies support a relationship between higher levels of CRP predicting hypertension. 3 In this issue of the journal, Li et al. 4 show that delivery of CRP via a single injection of adeno-associated virus (AAV) over expression of human CRP (AAVhCRP) vs. AAV-green fluorescent protein results in an increase of CRP upto 25 mg l À1 in Sprague-Dawley rats. Coupled with this increased CRP, they show an increase in both systolic and intra-arterial blood pressure (BP). In an attempt to elucidate the molecular mechanisms, they show an increase in reactive oxygen species possibly due to increased NADPH oxidase activity and decreased SOD1, decreased eNOS and an increase in Rho kinase. All these suggested mechanisms could result in an increase in hypertension. This study follows a previous report in which Guan et al. 5 reported that a single injection of AAV-hCRP into male Wistar rats resulted in efficient sustained expression of CRP in the liver, together with an increase in serum CRP to 15 mg l À1 at 2-4 months compared with AAV-green fluorescent protein. Most importantly in this paper, they also showed that human CRP resulted in an increase in systolic and mean arterial pressure. Collectively in these papers, results showed that in addition to impaired vasoreactivity, there was an increase in the expression of angiotensin-1 (AT-1) receptors, endothelin-1 and the ETA type-1 receptors. They also showed a decreased expression of eNOS and AT-2 receptors. This was accompanied by impairment in endotheliumdependent vasorelaxation.Previously, Vongpatanasin et al. 6 reported that CRP induces hypertension in CF1 transgenic mice expressing rabbit CRP (CF1-CRP) under the regulation of the phosphoenolpyruvate carboxykinase promoter, compared with wild-type CF1 control. CRP levels attained were about 10-15 mg l À1 . It should be emphasized, however, that unlike the current study and the study by Guan et al., 5 they suggested this effect was not attributable to the effect of theAT-1 receptor, which was unaltered, but to a decrease in the AT-2 receptor. However, the study by Vongpatanasin et al. 6 provided little further information with regard to molecular insights.Recently, Pravanec et al. 7 reported that in spontaneously hypertensive rats, human CRP under the control of the apolipoprotein E promoter resulted in a substantial increase in human CRP levels. This increase in CRP resulted in an increase in both systolic and diastolic BPs measured by telemetry, compared with the spontaneously hypertensive rat controls. They suggest in their paper ...

Identifying Biomarker Patterns and Predictors of Inflammation and Myocardial Stress

“…29 Hypertension and hsCRP have also been associated in other studies due to shared mechanisms of oxidative stress and endothelial dysfunction. 30 Specifically, hsCRP is known to attenuate nitric oxide production and decrease endothelial nitric oxide synthase expression leading to vasoconstriction and atherothrombosis. 20 The association between elevated hsCRP and hypertension is consistent across multiple racial and ethnic groups.…”

Human C-reactive protein induces endothelial dysfunction in biobreeding diabetic rats

“…Endothelial vasodilatation is mediated by both prostacyclin and nitric oxide. 11,17 It has been demonstrated previously that hCRP decreases eNOS activity and significantly decreases release of prostacyclin in vitro in human aortic endothelial cells (HAEC) contributing to endothelial dysfunction. 21 Hein et al 22 showed significantly decreased eNOS activity in vivo in Sprague Dawley rats injected with hCRP.…”

“…Various reports point towards a role of CRP in mediating endothelial dysfunction including increase in ET-1, PAI-1, cell adhesion molecules (CAM) [such as ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin], macrophage colony stimulating factor (M-CSF) and monocyte chemotactic protein-1 (MCP-1) and decrease in levels of prostacyclin, tissue plasminogen activator (tPA) and endothelial nitric oxide synthase (eNOS) activity. 11,17…”

Joint effect of elevated-c-reactive protein level and hypertension on new-onset stroke: A nationwide prospective cohort study of CHARLS

“…Several explanations have been put forward to explain the possible underlying mechanisms. Hypertension may promote inflammation of the blood vessels by increasing mechanical stress on arterial walls ( 30 ) and normal CRP levels could be prevented against hypertension in animal models and humans ( 31 , 32 ). There are many mechanisms by which CRP levels may increase BP by regulating many molecules released from endothelial cells.…”