PM2.5 promotes plaque vulnerability at different stages of atherosclerosis and the formation of foam cells via TLR4/MyD88/NFκB pathway.

Clinical evidence has shown an elevated myocardial infarction (MI) risk after PM2.5 (particulate matter < 2.5 µm) exposure. Incident MI may result from rupture of vulnerable plaques. To test whether PM2.5 could promote plaque vulnerability, we exposed PM2.5 to apoe-/- mice by intranasal instillation. We detected the lipid, collagen, macrophage and smooth muscle cells (SMCs) content, and fibrous cap thickness to evaluate the plaque vulnerability. Plaques in HFD-fed mice with PM2.5 treatment for 24 weeks had increased lipid content and macrophage recruitment, and reduced collagen content, fibrous cap thickness and SMCs infiltration. Besides, 4-week exposure to PM2.5 could reduce the fibrous cap thickness, collagen content, but increase the macrophage infiltration and SMCs loss in a rapid atherosclerosis model. In existing plaques, PM2.5 could also decrease the fibrous cap thickness, collagen content. In RAW264.7, PM2.5 could promote the transformation of macrophage into foam cells. The expression of TLR4/MyD88/NFκB and CD36 were upregulated by PM2.5 treatment. Besides, the expression of CD36 promoted by PM2.5 was downregulated by the TLR4 inhibitor or MyD88/NFκB SiRNA. In conclusion, our data indicated that short- and long-term PM2.5 exposure increased plaque vulnerability. The underlying mechanism might be the PM2.5-enhanced formation of foam cells via TLR4/MyD88/NFκB pathway.

Comparison of the effects of selective and non-selective His bundle pacing on cardiac electrical and mechanical synchrony.

Aims: This study aimed to assess the acute effect of selective His bundle pacing (S-HBP), non-selective His bundle pacing (NS-HBP), and right ventricular septum pacing (RVSP) on electrical synchrony and left ventricular (LV) mechanical synchrony using electrocardiogram and phase analysis of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Methods and results: Totally 39 patients eligible for pacemaker were enrolled. Thirty-seven patients underwent successful His bundle pacing (HBP) including S-HBP in 23 and NS-HBP in 14 patients, respectively. Thirty-one patients simultaneously underwent backup RVSP. Twenty-three patients received SPECT MPI scans under different pacing modes, including S-HBP low- and high-output, NS-HBP low- and high-output, and RVSP mode. The paced QRS duration (QRSd) in the S-HBP low- and high-output mode and in the NS-HBP high-output mode were similarly compared with the baseline intrinsic QRSd. QRS duration in the NS-HBP low-output mode was slightly longer than the baseline. QRS duration was the longest in the RVSP group. Left ventricular mechanical synchrony parameters in both the S-HBP and the NS-HBP groups were remarkably better than those in the RVSP group. Moreover, LV mechanical synchrony parameters were much better in the S-HBP groups and NS-HBP high-output group. Conclusion: Selective His bundle pacing and high-output NS-HBP could restore normal electrical and LV mechanical synchrony.

Colchicine for prevention of post-operative atrial fibrillation: Meta-analysis of randomized controlled trials.

Objective: This study intended to assess the efficacy of colchicine for prevention of post-operative atrial fibrillation (AF). Background: Post-operative AF is a common complication of surgery operations. Inflammation plays a crucial role in the pathogenesis of post-operative AF. Colchicine, a potent anti-inflammatory drug, may have a role in mitigating the incidence of post-operative AF. Methods: We searched Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Database of Chinese sci-tech periodicals (COVIP), and Wanfang Database for randomized controlled trials (RCTs) comparing colchicine versus placebo, or usual care for prevention of post-operative AF. The main outcome was the occurrence of AF post operation, which includes cardiac surgery, lung surgery, or pulmonary vein isolation. The estimated risk ratio (RR) for the occurrence of post-operative AF was evaluated using a random-effects model. The safety end point was the development of any side effects. Results: A total of 12 RCTs with 2274 patients were eventually included in this meta-analysis, where 1141 patients received colchicine and 1133 patients received placebo or usual care. Perioperative colchicine treatment was related to a decreased incidence of post-operative AF (RR: 0.65; 95% confidence interval [CI]: 0.56 to 0.75, p<0.001). Although the incidence of gastrointestinal side effects was increased with colchicine therapy when compared to placebo (RR = 2.49, 95% CI 1.85 to 3.34, p < 0.001), the incidence of major adverse events was not increased (RR = 0.86, 95% CI 0.46 to 1.60, p = 0.64). Conclusion: In conclusion, the results of our meta-analysis suggest that colchicine treatment could lower the incidence of post-operative AF. Further studies are needed to determine the optimal colchicine treatment regime to minimize the incidence of adverse events.

CTRP1 Aggravates Cardiac Dysfunction Post Myocardial Infarction by Modulating TLR4 in Macrophages.

CTRP1 (C1q/TNF-α [tumour necrosis factor-α]-related protein 1), an adiponectin paralog, is associated with diabetes and adverse events in cardiovascular disease. However, its effect on cardiac function post myocardial infarction (MI) is unclear. Our study aimed to explore the role of CTRP1 in cardiac function post MI. CTRP1 global knockout mice were subjected to left anterior descending ligation to establish the MI model. C57BL6J mice were also administered recombinant CTRP1 protein (200 µg/kg) 7 days post MI. As a result, mice with CTRP1 deficiency exhibited an increased survival rate, a reduced infarct area, improved cardiac function and decreased inflammation and oxidative stress levels at 4 weeks post MI compared with those of mice receiving the CRTP1 injection, whose conditions deteriorated. However, cardiomyocytes with either CTRP1 silencing or CTRP1 treatment showed few differences in inflammation and oxidative stress levels compared with those of the control under hypoxic conditions. The activation of macrophages isolated from CTRP1-deficient mice was decreased in response to interferon-γ, while CTRP1 enhanced the activation of macrophages in response to interferon-γ. Macrophage scavengers and clodronate liposomes antagonized the effects of CTRP1 injection in mice. We also found that CTRP1 regulated macrophage activation via adiponectin receptor 1, which binds to TLR4 on the macrophage membrane. TLR4 knockout also antagonized the effects of the CTRP1 protein on mice with MI. Taken together, these data indicate that CTRP1 supresses cardiac function post MI via TLR4 on macrophages. Targeting CTRP1 may become a promising therapeutic approach to cardiac dysfunction post MI.