Air pollution exerts several deleterious effects on the cardiovascular system, with cardiovascular disease (CVD) accounting for 80% of all premature deaths caused by air pollution. Short-term exposure to particulate matter 2.5 (PM_2.5) leads to acute CVD-associated deaths and nonfatal events, whereas long-term exposure increases CVD-associated risk of death and reduces longevity. Here, we summarize published data illustrating how PM_2.5 may impact the cardiovascular system to provide information on the mechanisms by which it may contribute to CVDs. We provide an overview of PM_2.5, its associated health risks, global statistics, mechanistic underpinnings related to mitochondria, and hazardous biological effects. We elaborate on the association between PM_2.5 exposure and CVD development and examine preventive PM_2.5 exposure measures and future strategies for combating PM_2.5-related adverse health effects. The insights gained can provide critical guidelines for preventing pollution-related CVDs through governmental, societal, and personal measures, thereby benefitting humanity and slowing climate change.

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear family of ligand activated transcriptional factors and comprise three different isoforms, PPAR-α, PPAR-β/δ, and PPAR-γ. The main role of PPARs is to regulate the expression of genes involved in lipid and glucose metabolism. Several studies have demonstrated that PPAR agonists improve dyslipidemia and glucose control in animals, supporting their potential as a promising therapeutic option to treat diabetes and dyslipidemia. However, substantial differences exist in the therapeutic or adverse effects of specific drug candidates, and clinical studies have yielded inconsistent data on their cardioprotective effects. This review summarizes the current knowledge regarding the molecular function of PPARs and the mechanisms of the PPAR regulation by posttranslational modification in the heart. We also describe the results and lessons learned from important clinical trials on PPAR agonists and discuss the potential future directions for this class of drugs.

Background: In the current era of mechanical circulatory support, limited data are available on prognosis of cardiogenic shock (CS) caused by various diseases. We investigated the characteristics and predictors of in-hospital mortality in Korean patients with CS. Methods: The RESCUE study (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With CS) is a multicenter, retrospective, and prospective registry of patients that presented with CS. Between January 2014 and December 2018, 1247 patients with CS were enrolled from 12 major centers in Korea. The primary outcome was in-hospital mortality. Results: In-hospital mortality rate was 33.6%. The main causes of shock were ischemic heart disease (80.7%), dilated cardiomyopathy (6.1%), myocarditis (3.2%), and nonischemic ventricular arrhythmia (2.5%). Vasopressors were used in 1081 patients (86.7%). The most frequently used vasopressor was dopamine (63.4%) followed by norepinephrine (57.3%). An intraaortic balloon pump was used in 314 patients (25.2%) and extracorporeal membrane oxygenator in 496 patients (39.8%). In multivariable analysis, age ≥70years (odds ratio [OR], 2.73 [95% CI, 1.89–3.94], P <0.001), body mass index <25 kg/m ² (OR, 1.52 [95% CI, 1.08–2.16], P =0.017), cardiac arrest at presentation (OR, 2.16 [95% CI, 1.44–3.23], P 80 (OR, 3.55 [95% CI, 2.54–4.95], P <0.001), requiring continuous renal replacement therapy (OR, 4.14 [95% CI, 2.88–5.95], P <0.001), mechanical ventilator (OR, 3.17 [95% CI, 2.16–4.63], P <0.001), intraaortic balloon pump (OR, 1.55 [95% CI, 1.07–2.24], P =0.020), and extracorporeal membrane oxygenator (OR, 1.85 [95% CI, 1.25–2.76], P =0.002) were independent predictors for in-hospital mortality. Conclusions: The in-hospital mortality of patients with CS remains high despite the high utilization of mechanical circulatory support. Age, low body mass index, cardiac arrest at presentation, amount of vasopressor, and advanced organ failure requiring various support devices were poor prognostic factors for in-hospital mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02985008.

NAD(P)H:quinone oxidoreductase (NQO) is an antioxidant flavoprotein that catalyzes the reduction of highly reactive quinone metabolites by employing NAD(P)H as an electron donor. There are two NQO enzymes—NQO1 and NQO2—in mammalian systems. In particular, NQO1 exerts many biological activities, including antioxidant activities, anti-inflammatory effects, and interactions with tumor suppressors. Moreover, several recent studies have revealed the promising roles of NQO1 in protecting against cardiovascular damage and related diseases, such as dyslipidemia, atherosclerosis, insulin resistance, and metabolic syndrome. In this review, we discuss recent developments in the molecular regulation and biochemical properties of NQO1, and describe the potential beneficial roles of NQO1 in diseases associated with oxidative stress.

The insulin-like growth factor 1 receptor (IGF-1R) signaling in cardiomyocytes is implicated in physiological hypertrophy and myocardial aging. Although fibroblasts account for a small amount of the heart, they are activated when the heart is damaged to promote cardiac remodeling. However, the role of IGF-1R signaling in cardiac fibroblasts is still unknown. In this study, we investigated the roles of IGF-1 signaling during agonist-induced cardiac fibrosis and evaluated the molecular mechanisms in cultured cardiac fibroblasts. Using an experimental model of cardiac fibrosis with angiotensin II/phenylephrine (AngII/PE) infusion, we found severe interstitial fibrosis in the AngII/PE infused myofibroblast-specific IGF-1R knockout mice compared to the wild-type mice. In contrast, low-dose IGF-1 infusion markedly attenuated AngII-induced cardiac fibrosis by inhibiting fibroblast proliferation and differentiation. Mechanistically, we demonstrated that IGF-1-attenuated AngII-induced cardiac fibrosis through the Akt pathway and through suppression of rho-associated coiled-coil containing kinases (ROCK)2-mediated α-smooth muscle actin (αSMA) expression. Our study highlights a novel function of the IGF-1/IGF-1R signaling in agonist-induced cardiac fibrosis. We propose that low-dose IGF-1 may be an efficacious therapeutic avenue against cardiac fibrosis.

BACKGROUND: The RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) demonstrated that intravascular imaging–guided percutaneous coronary intervention (PCI) improved clinical outcome compared with angiography-guided PCI for patients with complex coronary artery lesions. This study aims to assess whether the prognostic benefit of intravascular imaging–guided procedural optimization persists in patients undergoing PCI for left main coronary artery disease. METHODS: Of 1639 patients enrolled in the RENOVATE-COMPLEX-PCI, 192 patients with left main coronary artery disease were selected for the current prespecified substudy. Selected patients were randomly assigned to either the intravascular imaging–guided PCI group (n=138) or the angiography-guided PCI group (n=54). The primary end point was target vessel failure defined as a composite of cardiac death, target vessel–related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: At a median follow-up of 2.1 years (interquartile range 1.1 to 3.0 years), intravascular imaging–guided PCI was associated with lower incidence of primary end point compared with angiography-guided PCI (6.8% versus 25.1%; hazard ratio, 0.31 [95% CI, 0.13–0.76]; P =0.010). This significant reduction in primary end point was mainly driven by a lower risk of cardiac death or spontaneous target vessel–related myocardial infarction (1.6% versus 12.7%; hazard ratio, 0.16 [95% CI, 0.03–0.82]; P =0.028). Intravascular imaging–guided PCI was independently associated with a lower risk of primary end point, even after adjusting for various clinical factors (hazard ratio, 0.29 [95% CI, 0.12–0.72]; P =0.007). CONCLUSIONS: Intravascular imaging–guided PCI showed clinical benefit over angiography-guided PCI for left main coronary artery disease in reducing the risk of cardiac death, target vessel–related myocardial infarction, or target vessel revascularization. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03381872.