This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair.

No abstract

No abstract

Background Myocardial infarction with nonobstructive coronary arteries ( MINOCA ) is a heterogeneous disease entity. Its prognosis and predictor of mortality remain unclear. This study aimed to compare the prognosis between MINOCA and myocardial infarction with obstructive coronary artery disease and identify factors related to all‐cause death in MINOCA using a nation‐wide, multicenter, and prospective registry. Methods and Results Among 13 104 consecutive patients enrolled, patients without previous history of significant coronary artery disease who underwent coronary angiography were selected. The primary outcome was 2‐year all‐cause death. Secondary outcomes were cardiac death, noncardiac death, reinfarction, and repeat revascularization. Patients with MINOCA (n=396) and myocardial infarction with obstructive coronary artery disease (n=10 871) showed similar incidence of all‐cause death (9.1% versus 8.8%; hazard ratio [ HR ], 1.04; 95% CI, 0.74–1.45; P =0.83). Risks of cardiac death, noncardiac death, and reinfarction were not significantly different between the 2 groups ( HR , 0.82; 95% CI , 0.53–1.28; P =0.38; HR , 1.55; 95% CI , 0.93–2.56; P =0.09; HR , 1.23; 95% CI , 0.65–2.31; P =0.38, respectively). MINOCA patients had lower incidence of repeat revascularization (1.3% versus 7.2%; HR , 0.17; 95% CI , 0.07–0.41; P <0.001). Results were consistent after multivariable regression and propensity‐score matching. In a multivariate model, several significant predictors of all‐cause death of MINOCA were found, including the nonuse of renin‐angiotensin system blockers ( HR , 2.63; 95% CI , 1.08–6.25; P =0.033) and statins ( HR , 2.17; 95% CI , 1.04–4.54; P =0.039). Conclusions Patients with MINOCA and those with myocardial infarction with obstructive coronary artery disease had comparable clinical outcomes. Use of renin‐angiotensin system blockers and statins was associated with lower mortality in patients with MINOCA .

Aims  Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial. Methods and results  We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10−54; CES1 G143E, P = 1.3 × 10−16; CYP2C19*17, P = 9.5 × 10−10; CYP2B6 1294 + 53 C &gt; T, P = 3.0 × 10−4; CYP2B6 516 G &gt; T, P = 1.0 × 10−3; CYP2C9*2, P = 1.2 × 10−3; and CYP2C9*3, P = 1.5 × 10−3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14–2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35–14.27, P = 0.01) compared to patients who carried six or fewer of these alleles. Conclusion  Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.

No abstract

Objective-To investigate the effects of pioglitazone (PIO), a peroxisome proliferator-activated receptor ␥ agonist, on plaque matrix metalloproteinase (MMP) and macrophage (Mac) responses in vivo in a molecular imaging study. Methods and Results-In vitro, PIO suppressed MMP-9 protein expression in murine peritoneal Macs (PϽ0.05). To assess PIO's effects on plaque inflammation, nondiabetic apolipoprotein E Ϫ/Ϫ mice receiving a high-cholesterol diet (HCD) were administered an MMP-activatable fluorescence imaging agent and a spectrally distinct Mac-avid fluorescent nanoparticle. After 24 hours, mice underwent survival dual-target intravital fluorescence microscopy of carotid arterial plaques. These mice were then randomized to HCD or HCD plus 0.012% PIO for 8 weeks, followed by a second intravital fluorescence microscopy study of the same carotid plaque. In the HCD group, in vivo MMP and Mac target-to-background ratios increased similarly (PϽ0.01 versus baseline). In contrast, PIO reduced MMP and Mac target-to-background ratios (PϽ0.01) versus HCD. Changes in MMP and Mac signals correlated strongly (r Ն0.75). Microscopy demonstrated MMP and Mac reductions in PIO-treated mice and a PIO-modulated increase in plaque collagen. Conclusion-Serial optical molecular imaging demonstrates that plaque MMP and Mac activity in vivo intensify with hypercholesterolemia and are reduced by PIO therapy.

Blood transcriptome reflects the status of diseases, and characteristic molecular signature provides a novel window on gene expression preceding acute coronary events. We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI). We obtained peripheral blood from the patients with ACS who visited emergency department within 4 hours after the onset of chest pain: STEMI (n = 10), Non-ST-segment-elevation MI (NSTEMI, n = 10) and unstable angina (UA, n = 11). Blood transcriptome scans revealed that a characteristic gene expression change exists in STEMI, resulting in 531 outlier genes as STEMI molecular signature (Welch's t test, P < 0.05). Another analysis with a set of blood samples of patients with STEMI (n = 7) before and 7 days after the primary percutaneous coronary intervention (n = 7) and normal control (n = 10) evidenced that STEMI molecular signature directly reflects the onset of STEMI pathogenesis. From the two sets of transcriptome-based STEMI signatures, we identified 10 genes encoding transmembrane or secretory proteins that are highly expressed in STEMI. We validated blood protein expression levels of these 10 putative biomarkers in 40 STEMI and 32 healthy subjects by ELISA. Data suggested that PGLYRP1, IRAK3 and VNN3 are more specific and sensitive diagnostic biomarkers for STEMI than traditional CK-MB or troponin.Blood transcriptome scans of ACS evidenced early stage molecular markers for STEMI. Here, we report novel biomarkers to diagnose STEMI at emergency department in hospitals by a simple ELISA method.