Purinergic 2X7 receptor (P2X7R) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) are expressed in macrophages in atherosclerotic lesions. However, the mechanisms through which P2X7R participates in the inflammatory response in atherosclerosis remain largely unknown. The aim of the present study was to investigate the role of P2X7R in atherosclerosis and the mechanisms of action of the NLRP3 inflammasome following stimulation with oxidized low-density lipoprotein (oxLDL). We observed the expression and distribution of P2X7R in the atherosclerotic plaque in the coronary arteries from an autopsy specimen and in that of the aortic sinuses of apoE−/− mice by immunohistochemistry and immunofluorescence staining. The specificity of short interfering RNA (siRNA) was used to suppress P2X7R and NLRP3 mRNA expression. RT-qPCR and western blot analysis were used to analyze mRNA and protein expression, respectively. Co-immunoprecipitation was used to examine the interaction between protein kinase R (PKR) phosphorylation and NLRP3. P2X7R and NLRP3 were expressed at high levels in the atherosclerotic plaque in the coronary arteries. Stimulation with oxLDL upregulated P2X7R, NLRP3 and interleukin (IL)-1β expression. P2X7R knockdown by siRNA suppressed NLRP3 inflammasome activation by inhibiting the PKR phosphorylation mediated by oxLDL. In the atherosclerotic lesions in the aortic sinuses of apoE−/− mice, P2X7R expression was found at high levels. Moreover, P2X7R siRNA attenuated the development of atherosclerosis in the apoE−/− mice. In conclusion, our results demonstrate that P2X7R plays a significant role in the development of atherosclerosis and regulates NLRP3 inflammasome activation by promoting PKR phosphorylation.

We decided to assess the prognostic value of NLRP3 inflammasome level in acute coronary syndrome (ACS) patients and whether it was related to coronary atherosclerotic severity. Study population included one-hundred and twenty-three (123) subjects. Peripheral blood monocyte NLRP3 protein level was correlated with clinical presentation, angiographic characteristics and its scoring systems as well as GRACE and TIMI risk scores. Follow-up for major adverse cardiac events (MACE) was carried out at 180 days. Peripheral blood monocyte NLRP3 was found to be elevated in ACS patients (P < 0.05) and showed positive correlation with GRACE score (r = 0.619), TIMI score (r = 0.580), SYNTAX score (r = 0.550), Clinical SYNTAX score (r = 0.564) and Gensini score (r = 0.516). NLRP3 was also increased with increasing number of vessels, the number of lesions present and the presence bifurcation lesions (P < 0.05). Multivariate Cox regression analysis showed NLRP3 to be an independent predictor of MACE (P = 0.043). Kaplan-Meier analysis and receiver operating characteristic curves for NLRP3 showed good predictive value for MACE. There is a positive correlation of NLRP3 level with severity of coronary atherosclerosis. NLRP3 level is a promising prognostic utility and is efficient in event prediction for MACE.

NLRP3 is involved in inflammation that leads to atherosclerosis. A high dose of rosuvastatin can modulate the inflammatory process of atherosclerosis by downregulating the expression of NLRP3, cathepsin-B, and their downstream mediators. These findings provide insight into the pathogenesis and management of acute coronary syndrome, with NLRP3 as the potential target.

Hyper-homocysteinemia has positive correlation with coronary artery disease among young adults in the absence of conventional risk factors.

Objective: There is very limited data about gender based differences in Acute Coronary Syndrome (ACS) in Asian population. This study was therefore aimed to ascertain gender based differences in clinical and angiographic characteristics and clinical outcomes in patient admitted with ACS. Methods: This was a cross sectional, observational study including patients admitted with diagnosis of ACS. Patients were divided into two groups (Males and Females) and their clinical characteristics were noted. Gender based assessment was done following coronary angiography. Results: A total of 386 patients were included, with 210 males and 176 females. Anterior wall myocardial infarction (AWMI) was present in 177(45.86%) patients. Mean age was 72.8±12.9 years in females and 66.8±11.2 years in males. Diabetes was present in 38.1% females and 31% males. Patients from rural population were 225(58.3%), while from urban 161(41.7%). Mean ejection fraction was 43.9±7.9% in women and 38.2±8.68% in males. Conclusion: ACS was more common in males, rural population and AWMI was most common cause. Women were more elderly and had more adverse events as compared to males. Impaired renal dynamics were more commonly observed in males. Women were less aggressively treated with coronary interventions and radial approach was better tolerated regardless of gender. doi: https://doi.org/10.12669/pjms.35.5.743 How to cite this:Altaf A, Shah H, Salahuddin M. Gender based differences in clinical and Angiographic characteristics and outcomes of Acute Coronary Syndrome (ACS) in Asian population. Pak J Med Sci. 2019;35(5):---------. doi: https://doi.org/10.12669/pjms.35.5.743 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Recently, trimethylamine N-oxide (TMAO) unexplained gut microbe has been proposed as a promising risk factor for atherosclerotic cardiovascular disease (CVD) pathogenesis and adverse events. The relationship of TMAO with coronary atherosclerotic burden has been evaluated in patients with stable coronary artery disease and ST-segment elevation myocardial infarction, but still needs to be explored in newly diagnosed non-ST-segment elevation myocardial infarction (NSTEMI) patients. Material and methods: A prospective, single-center, SZ-NSTEMI trial (ChiCTR1900022366) is underway to investigate the relationship of TMAO with the severity and prognosis of coronary atherosclerosis in newly diagnosed NSTEMI patients who will undergo coronary angiography with primary percutaneous coronary intervention (pPCI). The primary endpoint of the study will be assessed the association of TMAO with coronary atherosclerotic severity quantify by the number of diseased coronary arteries and SYNTAX score after the coronary angiography. The secondary endpoints will be identified the TMAO as a prognostic biomarker for the short (1 month) and long-term (12 months) major cardiovascular and cerebrovascular events (MACCEs) rate including myocardial infarction, target vessel revascularization, stroke, heart failure, all-cause rehospitalization, and all-cause mortality after the pPCI. The blood samples will be collected from each patient before the procedure to measure the TMAO by isotope dilution high-performance liquid chromatography. In conclusion, SZ-NSTEMI will be the first cohort that will be investigated the association of TMAO with the severity and prognosis of coronary atherosclerotic burden in NSTEMI patients, aiming to identify TMAO as a predictor and a prognostic biomarker.

Background: Cardiac pacemaker infections have increased globally due to increase in demand and lack of adequate knowledge about its significantly contributing risk factors. This study was therefore aimed to determine the prevailing causative microbes and risk factors of both single and dual chamber permanent pacemaker infections. Methods: This was a retrospective case control study. Cases were selected as culture positive swab, Temporary pacemaker wire or catheter were matched with three controls for each variable using chi square test. Multivariate regression analysis was done to determine risk factors. Results: Among 47 cases, 23.4% cases were infected by methicillin resistant staph aureus, 14.9% by methicilin susceptible Staphylococcus aureus, 10.6% by pseudomonas, 8.5% by escherichia coli and 6.4% by klebsiella. Temporary pacemaker/Central line placed >24 hours ago before permanent pacemaker implantation, remnant pacemaker leads, corticosteroid use, no antibiotic prophylaxis, diabetes, smoking and non-absorbable stitches had statistically significant association with permanent pacemaker infection using multivariate regression model analysis. Chronic obstructive pulmonary disease and non-absorbable stitches had a non-significant association. Conclusions: Temporary pacemaker/Central line placed >24hours before permanent pacemaker implantation, remnant pacemaker leads, corticosteroid use, no antibiotic prophylaxis, diabetes, smoking and use of non-absorbable stitches are risk factors for permanent pacemaker infection. Staph aureus is the most prevalent microorganism causing infection.Keywords: Causes; dual chamber; Infectison; permanent pacemaker; risk factor; single chamber.

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