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Cardiac hypertrophy is an adaptive response of the myocardium to pressure overload or adrenergic agonists. Here, we investigated the protective effects and the regulatory mechanism of protocatechuic acid, a phenolic compound, using a mouse model of isoproterenol-induced cardiac hypertrophy. Our results demonstrated that protocatechuic acid treatment significantly downregulated the expression of cardiac hypertrophic markers (Nppa, Nppb, and Myh7), cardiomyocyte size, heart weight to body weight ratio, cross-sectional area, and thickness of left ventricular septum and posterior wall. This treatment also reduced the expression of isoproterenol-induced ROCK1, Sp1, and PKCγ both in vivo and in vitro. To investigate the mechanism, we performed knockdown and overexpression experiments. The knockdown of ROCK1, Sp1, or PKCγ decreased the isoproterenol-induced cell area and the expression of hypertrophic markers, while the overexpression of Sp1 or PKCγ increased the levels of hypertrophic markers. Protocatechuic acid treatment reversed these effects. Interestingly, the overexpression of Sp1 increased cell area and induced PKCγ expression. Furthermore, experiments using transcription inhibitor actinomycin D showed that ROCK1 and Sp1 suppression by protocatechuic acid was not regulated at the transcriptional level. Our results indicate that protocatechuic acid acts via the ROCK1/Sp1/PKCγ axis and therefore has promising therapeutic potential as a treatment for cardiac hypertrophy.

Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. Here, we investigated the clinical predictive value of serum CatK levels in patients with chronic heart failure (CHF). We examined 134 patients with CHF, measuring their serum CatK, troponin I, high-sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic peptide levels. The patients were divided into two groups: the 44 patients who showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the “lowLVEF” group) and the 90 patients showing LVEF values ≥ 40% (the “highLVEF” group). The lowLVEF patients had significantly higher serum CatK levels compared to the highLVEF patients (58.4 ± 12.2 vs. 44.7 ± 16.4, P < 0.001). Overall, a linear regression analysis showed that CatK levels correlated negatively with LVEF (r = −0.4, P < 0.001) and positively with LV end-diastolic dimensions (r = 0.2, P < 0.01), LV end-systolic dimensions (r = 0.3, P < 0.001), and left atrial diameters (r = 0.3, P < 0.01). A multiple logistic regression analysis showed that CatK levels were independent predictors of CHF (odds ratio, 0.90; 95% confidence interval, 0.84–0.95; P < 0.01). These data indicate that elevated levels of CatK are closely associated with the presence of CHF and that the measurement of circulating CatK provides a noninvasive method of documenting and monitoring the extent of cardiac remodeling and dysfunction in patients with CHF.

Background/Aims We aimed to evaluate the prevalence, characteristics, and clinical outcomes of spontaneous coronary artery dissection (SCAD) in young female patients with acute myocardial infarction (AMI). Methods We identified 8,250 patients diagnosed with AMI who underwent coronary angiogram from the Chonnam National University Hospital database, Gwangju, Korea, between November 2005 and September 2017. A total of 148 female patients aged less than 60 years with a history of AMI were retrospectively studied and the characteristics and clinical outcomes were evaluated for all SCAD patients. Results Among female patients with AMI aged less than 60 years, the prevalence of SCAD was 8.78% (13 of 148). Based on the angiographic classification, type 2 SCAD was most commonly observed on angiograms in 69.2% of the cases (nine of 13), followed by type 3 in 23.1% (three of 13), and type 1 in 7.7% (one of 13). Furthermore, the left anterior descending (LAD) artery was the most commonly affected coronary artery (76.9%, 10 of 13 cases) and the distal segments of the coronary arteries were the most common sites of SCAD (92.3%, 12 of 13). Regarding the clinical outcomes, one of 13 patients experienced repeat revascularization during the following 31 months. Conclusions The prevalence of SCAD was 8.7%, indicating that SCAD is not rare, among female patients aged less than 60 years with AMI in Korea. Type 2 SCAD was most commonly observed on angiogram. Moreover, the distal portion of the LAD was the segment most commonly affected by SCAD. The long-term clinical outcomes were favorable in patients surviving SCAD.

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