The peroxisome proliferator-activated receptor (PPAR)δ has been implicated in the pathogenesis of atherogenic disorders. However, its physiological roles and functions in vascular smooth muscle cells (VSMCs) remain relatively unclear. In the present study, we show that the gene encoding transforming growth factor (TGF)-β1 is a PPARδ target in VSMCs. The PPARδ activator GW501516 upregulates TGF-β1 expression in a dose- and time-dependent manner. This induction is attenuated significantly by the presence of small interfering RNA against PPARδ or GW9662, an inhibitor of PPARδ. Furthermore, activated PPARδ induces TGF-β1 promoter activity by binding to the direct repeat-1 response element TGF-β1–direct repeat-1. Mutations in the 5′ or 3′ half-sites of the response element totally abrogate transcriptional activation and PPARδ binding, which suggests that this site is a novel type of PPARδ response element. In addition, ligand-activated PPARδ attenuated the promoter activity and expression of monocyte chemoattractant protein-1 induced by interleukin-1β. These effects were significantly reduced in the presence of small interfering RNA against PPARδ, anti–TGF-β1 antibody, or a TGF-β type I receptor inhibitor. Decreased monocyte chemoattractant protein-1 expression induced by PPARδ was mediated by the effector of TGF-β1, Smad3. Finally, administration of GW501516 to mice upregulated TGF-β1, whereas the expression of proinflammatory genes including monocyte chemoattractant protein-1 was significantly attenuated in the thoracic aorta. Taken together, these results demonstrate the presence of a novel TGF-β1–mediated pathway in the antiinflammatory activities of PPARδ.

Atherothrombotic events are influenced by systemic hypercoagulability and fibrinolytic activity. The present study evaluated thrombogenicity indices and their prognostic implications according to disease acuity. From the consecutive patients undergoing percutaneous coronary intervention (PCI), those with thrombogenicity indices (n = 2705) were grouped according to disease acuity [acute myocardial infarction (AMI) vs. non-AMI]. Thrombogenicity indices were measured by thromboelastography (TEG). Blood samples for TEG were obtained immediately after insertion of the PCI sheath, and TEG tracing was performed within 4 h post-sampling. Major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) were evaluated for up to 4 years. Compared with non-AMI patients, AMI patients had higher platelet-fibrin clot strength [maximal amplitude (MA): 66.5 ± 7.8 vs. 65.3 ± 7.2 mm, P < 0.001] and lower fibrinolytic activity [clot lysis at 30 min (LY₃₀): 0.9 ± 1.8% vs. 1.1 ± 1.9%, P < 0.001]. Index AMI presentation was associated with MA [per one-mm increase: odds ratio (OR): 1.024; 95% confidence interval (CI): 1.013–1.036; P < 0.001] and LY₃₀ (per one% increase: OR: 0.934; 95% CI: 0.893–0.978; P = 0.004). The presence of high platelet-fibrin clot strength (MA ≥68 mm) and low fibrinolytic activity (LY₃₀ < 0.2%) was synergistically associated with MACE occurrence. In the multivariable analysis, the combined phenotype of ‘MA ≥ 68 mm’ and ‘LY₃₀ < 0.2%’ was a major predictor of post-PCI MACE in the AMI group [adjusted hazard ratio (HR): 1.744; 95% CI: 1.135–2.679; P = 0.011], but not in the non-AMI group (adjusted HR: 1.031; 95% CI: 0.499–2.129; P = 0.935). AMI occurrence is significantly associated with hypercoagulability and impaired fibrinolysis. Their combined phenotype increases the risk of post-PCI atherothrombotic event only in AMI patients. These observations may support individualized therapy that targets thrombogenicity for better outcomes in patients with AMI. Gyeongsang National University Hospital (G-NUH) Registry, NCT04650529. The association between thrombogenicity and AMI occurrence, and their prognostic implications for long-term cardiovascular outcomes were investigated. Abbreviations: AMI, acute myocardial infarction; HR, hazard ratio; LY30, percentage of the clot that has lysed 30 minutes after the time of maximum amplitude; MA, maximum amplitude; MACE, major adverse cardiovascular events; OR, odds ratio; PCI, percutaneous coronary intervention; TEG, thromboelastography.

Few studies have comprehensively presented epidemiological indicators of myocardial infarction in Korea. However, multiple published articles and open-source secondary data on the epidemiology of myocardial infarction are now available. This review summarized the hospitalization incidence, prevalence, and mortality rate of myocardial infarction in Korea using articles and open-source data from the Health Insurance Service and the Department of Statistics, surveys of sample populations, registries of patients, and other sources. The epidemiological indicators of myocardial infarction were compared between Korea and other high-income countries. The incidence of hospitalization due to myocardial infarction in Korea was 43.2 cases per 100,000 population in 2016 and has consistently increased since 2011. It was 2.4 times higher among men than among women. The estimated prevalence among adults over 30 years of age ranged from 0.34% to 0.70% in 2020; it was higher among men and increased with age. The mortality in 2020, which was 19.3 per 100,000 population in 2020, remained relatively stable in recent years. Mortality was higher among men than among women. Based on representative inpatient registry data, the proportion of ST-elevated myocardial infarction decreased until recently, and the median time from symptom onset to hospital arrival was approximately 2 hours and 30 minutes. The hospitalization incidence, prevalence, and mortality rate of myocardial infarction were lower in Korea than in other countries, although there was an increasing trend. Comprehensive national-level support and surveillance systems are needed to routinely collect accurate epidemiological indicators.

Kim RB, et al. J Korean Med Sci. 2019 Nov;34(50):e322. https://doi.org/10.3346/jkms.2019.34.e322

Sim DS, et al. Korean Circ J. 2019 Aug;50:e5. https://doi.org/10.4070/kcj.2019.0166