Curcumin regulates pulmonary extracellular matrix remodeling and mitochondrial function to attenuate pulmonary fibrosis by regulating the miR-29a-3p/DNMT3A axis.

Epigenetic regulation and mitochondrial dysfunction are essential to the progression of idiopathic pulmonary fibrosis (IPF). Curcumin (CCM) in inhibits the progression of pulmonary fibrosis by regulating the expression of specific miRNAs and pulmonary fibroblast mitochondrial function; however, the underlying mechanism is unclear. C57BL/6 mice were intratracheally injected with bleomycin (5 mg/kg) and treated with CCM (25 mg/kg body weight/3 times per week, intraperitoneal injection) for 28 days. Verhoeff-Van Gieson, Picro sirius red, and Masson's trichrome staining were used to examine the expression and distribution of collagen and elastic fibers in the lung tissue. Pulmonary fibrosis was determined using micro-computed tomography and transmission electron microscopy. Human pulmonary fibroblasts were transfected with miR-29a-3p, and RT-qPCR, immunostaining, and western blotting were performed to determine the expression of DNMT3A and extracellular matrix collagen-1 (COL1A1) and fibronectin-1 (FN1) levels. The expression of mitochondrial electron transport chain complex (MRC) and mitochondrial function were detected using western blotting and Seahorse XFp Technology. CCM in increased the expression of miR-29a-3p in the lung tissue and inhibited the DNMT3A to reduce the COL1A1 and FN1 levels leading to pulmonary extracellular matrix remodeling. In addition, CCM inhibited pulmonary fibroblasts MRC and mitochondrial function via the miR-29a-3p/DNMT3A pathway. CCM attenuates pulmonary fibrosis via the miR-29a-3p/DNMT3A axis to regulate extracellular matrix remodeling and mitochondrial function and may provide a new therapeutic intervention for preventing pulmonary fibrosis.

Endocardial Endothelial Dysfunction and Unknown Polymorphic Composite Accumulation in Heart Failure.

The accumulation of unknown polymorphic composites in the endocardium damages the endocardial endothelium (EE). However, the composition and role of unknown polymorphic composites in heart failure (HF) progression remain unclear. Here, we aimed to explore composite deposition during endocardium damage and HF progression. Adult male Sprague-Dawley rats were divided into two HF groups-angiotensin II-induced HF and left anterior descending artery ligation-induced HF. Heart tissues from patients who had undergone coronary artery bypass graft surgery (non-HF) and those with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) were collected. EE damage, polymorphic unknown composite accumulation, and elements in deposits were examined. HF progression reduced the expression of CD31 in the endocardium, impaired endocardial integrity, and exposed the myofibrils and mitochondria. The damaged endocardial surface showed the accumulation of unknown polymorphic composites. In the animal HF model, especially HF caused by myocardial infarction, the weight and atomic percentages of O, Na, and N in the deposited composites were significantly higher than those of the other groups. The deposited composites in the human HF heart section (DCM) had a significantly higher percentage of Na and S than the other groups, whereas the percentage of C and Na in the DCM and ICM groups was significantly higher than those of the control group. HF causes widespread EE dysfunction, and EndMT was accompanied by polymorphic composites of different shapes and elemental compositions, which further damage and deteriorate heart function.