Enhanced monocyte recruitment and delayed alternative macrophage polarization accompanies impaired repair following myocardial infarction in C57BL/6 compared to BALB/c mice.

Activation of the innate immune response following myocardial infarction (MI) is essential for infarct repair. Preclinical models of MI commonly use C57BL/6 mice, which have a type 1-dominant immune response, whereas other mouse strains such as BALB/c mice have a type 2-dominant immune response. We compared C57BL/6 and BALB/c mice to investigate whether predisposition towards a proinflammatory phenotype influences the dynamics of the innate immune response to MI and associated infarct healing and the risk of cardiac rupture. MI was induced by permanent coronary artery ligation in 12-15-week-old male wild-type BALB/c and C57BL/6 mice. Prior to MI, C57BL/6 mice had a lower proportion of CD206+ anti-inflammatory macrophages in the heart and an expanded blood pool of proinflammatory Ly6Chigh monocytes in comparison to BALB/c mice. The systemic inflammatory response in C57BL/6 mice following MI was more pronounced, with greater peripheral blood Ly6Chigh monocytosis, splenic Ly6Chigh monocyte mobilization and myeloid cell infiltration of pericardial adipose tissue. This led to an increased and prolonged macrophage accumulation, as well as delayed transition towards anti-inflammatory macrophage polarization in the infarct zone and surrounding tissues of C57BL/6 mice. These findings accompanied a higher rate of mortality due to cardiac rupture in C57BL/6 mice compared with BALB/c mice. We conclude that lower post-MI survival of C57BL/6 mice over BALB/c mice is mediated in part by a more pronounced and prolonged inflammatory response. Outcomes in BALB/c mice highlight the therapeutic potential of modulating resolution of the innate immune response following MI for the benefit of successful infarct healing.

Resident cells of the myocardium: more than spectators in cardiac injury, repair and regeneration.

Multiple resident cell types contribute to maintaining the structure and physiological function of the heart over the life course. Cardiomyocyte proliferation supports scar free regeneration in the neonatal heart following injury, but a lower rate of proliferation in the adult necessitates replacement by a collagen scar to maintain ventricular integrity. In this short review we discuss recent studies that have identified novel roles for non-myocyte resident cells and the extracellular matrix in supporting repair, as well as cardiomyocyte and vascular regeneration, following myocardial infarction.

Molecular imaging of the atherosclerotic plaque using positron emission tomography.

Accurately assessing an individual's risk of myocardial infarction or stroke using currently available risk stratification tools remains a challenge, even in patients with symptomatic disease. Inflammation, micro-calcification and intra-plaque angiogenesis occur during the development and ultimate rupture of vulnerable plaques. Molecular imaging techniques such as combined positron emission tomography and computed tomography (PET/CT) offer the opportunity to target these key cellular processes within atheroma and identify high-risk lesions. In this review we will set out the studies that have demonstrated the feasibility of PET/CT imaging in assessing atherosclerotic plaque inflammation, micro-calcification and angiogenesis. We will also discuss the potential of PET/CT molecular imaging as both a screening tool for novel therapeutic interventions and as a means of improving cardiovascular risk stratification.

Differences between South Asians and White Europeans in five year outcome following percutaneous coronary intervention.

AIMS: The aim of this study was to compare rates of target lesion revascularisation (TLR) and total mortality between South Asians (SAs) and White Europeans (WEs) following percutaneous coronary intervention (PCI). METHODS: We followed a cohort of 293 SAs and 865 WEs patients admitted for elective or urgent PCI to de novo lesions. For each patient, baseline cardiovascular risk factors and angiographic data were obtained. Patients had long-term follow-up for all-cause mortality and TLR. RESULTS: Patients were followed up over a median period of 54 months (inter-quartile range: 47-65). SAs were younger (62 ± 12 years vs. 66 ± 11 years; p < 0.0001), with a higher prevalence of diabetes, greater social deprivation [Carstairs score: 10.2 (IQR 6.5-12.1) vs. 3.3 (IQR 0.9-6.5); p < 0.0001] and presented more acutely (urgent PCI procedure). During the follow-up period, a total of 119 deaths and 111 TLR [94 repeat PCI and 17 coronary artery bypass grafting (CABG)] occurred. There was no significant difference in the rate of long-term all-cause mortality between SA and WE [31 (10.6%) vs. 107 (12.4%); OR: 0.84 (0.55-1.28); p = 0.47]. However, SA ethnicity was an independent predictor of long-term TLR, after adjusting for baseline clinical and procedural characteristics [54 (18.4%) vs. 57 (6.6%); OR: 2.83 (1.87-4.29); p < 0.0001]. CONCLUSIONS: South Asian patients were more likely to require re-admission to treat clinical restenosis of the index lesion. There was no significant long-term difference in all-cause mortality between SA and WE patients.

The -344T>C promoter variant of the gene for aldosterone synthase (CYP11B2) is not associated with cardiovascular risk in a prospective study of UK healthy men.

INTRODUCTION: The tissue renin-angiotensin system is implicated in the pathogenesis of coronary artery disease (CAD). As locally synthesised aldosterone is a potential mediator of CAD, we have sought an association of the -344T>C variant of the aldosterone synthase (CYP11B2) gene with CAD events. METHODS: Subjects comprised of the Second Northwick Park Heart Study (NPHSII), a prospective study of unrelated, healthy middle-aged Caucasian males. CAD events were recorded in 2490 subjects, and defined as a sudden cardiac death, myocardial infarction or coronary artery revascularisation procedure. Mean follow-up was 10.8 years. Aldosterone synthase genotype was determined in 2490 subjects. Power calculation suggests that we have 80% power (at a significance level of 0.05) to detect a difference in hazard ratio (HR) between homozygote groups of 0.45. RESULTS: One hundred and eighty-seven CAD events were recorded in 2490 subjects. In the group overall, CAD events were independent of genotype with adjusted hazard ratios being 1.00 versus 1.25 versus 0.80 for TT versus TC versus CC genotypes, respectively, P = 0.07. Genotype interactions with smoking and blood pressure were sought. Whilst CAD events were independent of genotype amongst non-smokers, CC genotype in smokers was associated with a reduced risk HR 2.02 versus 2.28 versus 0.82 for TT versus TC versus CC genotypes, P = 0.05 (HR for TT + TC versus CC were 1.77 versus 0.67, P = 0.02). This apparent interaction remained after adjustment for conventional risk factors. No such interaction was found with blood pressure. CONCLUSIONS: Aldosterone synthase genotype is unrelated to overall CAD events risk. A possible interaction with smoking requires confirmation.