Increasing evidence suggests that the NLRP3 (nucleotide oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome participates in cardiovascular diseases. However, its role and activation mechanism during hypertension remains unclear. In this study, we tested the role and mechanism of calcium-sensing receptor (CaSR) in NLRP3 inflammasome activation during hypertension. We observed that the expressions of CaSR and NLRP3 were increased in spontaneous hypertensive rats (SHRs) along with aortic fibrosis. In vascular smooth muscle cells (VSMCs), the activation of NLRP3 inflammasome associated with CaSR and collagen synthesis was induced by angiotensin II (Ang II). Furthermore, inhibition of CaSR and NLRP3 inflammasome attenuated proinflammatory cytokine release, suggesting that CaSR-mediated activation of the NLRP3 inflammasome may be a therapeutic target in aortic dysfunction and vascular inflammatory lesions.
Background: Mild elevation of serum cardiac troponin (Tn) reflects myocardial injury and is associated with cardiovascular events, even without overt cardiovascular disease. The purpose of this study was to investigate the possible mechanism of mild elevation of high-sensitivity cardiac troponin I (hs-cTnI) and its impact on prognosis in patients with non-obstructive coronary artery disease (CAD).Methods: 474 consecutive patients with suspected CAD and without significant coronary artery stenosis (<50%) who underwent adenosine triphosphate disodium (ATP) stress MCE were followed up (median, 41months) for endpoint events. Hs-cTnI was tested before MCE. Replenishment velocity (β), relative myocardial blood flow (rBV) and myocardial blood flow reserve (MBFR) were measured by stress MCE.Results: A total of 214 (45.1%) patients had hs-cTnI concentrations exceeding the limitation of detection (LOD) (0.001 ng/ml). Compared to patients with hs-cTnI below LOD, patients with higher hs-cTnI were older (p<0.05), had higher prevalence of atrial fibrillation (p<0.001) and lower MBFR (p<0.001). After adjustment, the association was still significant between detectable hs-cTnI and MBFR (odds ratio = 0.200; 95% CI: 0.043,0.923, P = .039). Detectable hs-cTnI was associated with endpoint events independent of MBFR (adjusted hazard ratio 8.927,95%CI 1.341-149.48, P=0.028). Hs-cTnI higher than LOD had greater cumulative event rate (log-rank P=0.004). The risk of incident endpoint events was greater for higher hs-cTnI (≥0.001 versus <LOD; adjusted hazard ratio, 13.398; 95% CI, 1.243, 144.371) (P<0.001).Conclusions: In patients with non-obstructive CAD, mild myocardial injury was associated with impaired myocardial perfusion as measured by quantitative MCE; both of them independently affect prognosis; low-level hs-cTnI elevation predicts adverse events independent of myocardial ischemia due to microvascular dilation dysfunction.
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