C-Reactive Protein Upregulates Angiotensin Type 1 Receptors in Vascular Smooth Muscle

Abstract

Background-Accumulating evidence suggests that C-reactive protein (CRP), in addition to predicting vascular disease, may actively facilitate lesion formation by inciting endothelial cell activation. Given the central importance of angiotensin type 1 receptor (AT 1 -R) in the pathogenesis of atherosclerosis, we examined the effects of CRP on AT 1 -R expression and kinetics in vascular smooth muscle (VSM) cells. In addition, the effects of CRP on VSM migration, proliferation, and reactive oxygen species (ROS) production were evaluated in the presence and absence of the angiotensin receptor blocker, losartan. Lastly, the effects of CRP (and losartan) on neointimal formation were examined in vivo in a rat carotid angioplasty model. Methods and Results-The effects of human recombinant CRP (0 to 100 g/mL) on AT 1 -R transcript, mRNA stability, and protein expression were studied in cultured human VSM cells. AT 1 -R binding was assessed with 125 I-labeled angiotensin II (Ang II). VSM migration was assessed with wound cell migration assays, whereas VSM proliferation was determined with [3 H]-incorporation and cell number. The effects of CRP (and losartan) on Ang II-induced ROS production were evaluated by 2Ј,7Ј-dichlorofluorescein fluorescence. Lastly, the effects of CRP (and losartan) on neointimal formation, VSM cell migration, proliferation, and matrix formation were studied in vivo in a rat carotid artery balloon injury model. CRP markedly upregulated AT 1 -R mRNA and protein expression and increased AT 1 -R number on VSM cells. CRP promoted VSM migration and proliferation in vitro and increased ROS production. Furthermore, CRP potentiated the effects of Ang II on these processes. In the rat carotid artery angioplasty model, exposure to CRP resulted in an increase in cell migration and proliferation, collagen and elastin content, and AT 1 -R expression, as well as an increase in neointimal formation; these effects were attenuated by losartan. Conclusions-CRP, at concentrations known to predict cardiovascular events, upregulates AT 1 -R-mediated atherosclerotic events in vascular smooth muscle in vitro and in vivo. These data lend credence to the notion that CRP functions as a proatherosclerotic factor as well as a powerful risk marker.

Systemic low-grade inflammation is related to both circulating and adipose tissue TNFα, leptin and IL-6 levels in obese women

“…2,3,9 CRP could be deleterious on the arterial wall since it has been found to promote directly endothelial cell inflammation and atherosclerotic processes. [23][24][25][26] Therefore, to reduce CRP levels could help to prevent vascular damage. This emphasizes the importance of weight loss programs in obese subjects since previous studies showed a significant reduction in proinflammatory adipocytokines and circulating hs-CRP levels after weight loss.…”

Relationships of C-reactive protein, uric acid, and glomerular filtration rate to arterial stiffness in Japanese subjects

“…Table 4 (a) What is known about this topic K CRP, UA, and ESRD are risk factors of cardiovascular diseases K But the relationships of CRP, UA, and GFR to arterial stiffness have not been fully investigated (b) What this study adds K CRP and UA are associated with an increase of arterial stiffness in male and female subjects K GFR is possibly related to arterial stiffness in male subjects C-reactive protein, uric acid, glomerular filtration, and arterial stiffness Y Saijo et al vascular remodeling and stiffen the artery. Wang et al 31 showed that CRP upregulated angiotensin type 1 receptor on vascular smooth muscle cells and promoted vascular smooth muscle cell migration and proliferation and reactive oxygen species production, and increased collagen and elastin contents, which might cause arterial stiffness, too.…”

Inflammatory markers are associated with left ventricular hypertrophy and diastolic dysfunction in a population-based sample of elderly men and women

“…It is possible that CRP could induce direct myocardial effects, as CRP can cause intimal hypertrophy both in vitro and in animal studies. 27,28 Alternatively, such effects may be indirect as studies of transgenic mice have associated CRP with the development of hypertension 29 and perivascular fibrosis. 30 The relationship between CRP genotype and human LVH was investigated for the first time in a study by Mann et al 31 They observed an association between a variant of the CRP gene with exercise-induced LVH in young healthy males, undergoing an identical 12-week physical training program.…”