Optimized new Shengmai powder inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway.

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder (, ONSMP) on myocardial fibrosis in heart failure (HF) based on rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinases (ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham (n = 10) and operation (n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low (L), medium (M), and high (H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen (COL) I and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the mRNA levels of COL I, COL Ⅲ, α-smooth muscle actin (α-SMA), and c-Fos proto-oncogene (c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor (p-ELK1), p-c-Fos, α-SMA, COL I, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL I/Ⅲ content, down-regulate the mRNA of COL I/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/ 2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

Biomarkers in heart failure: the past, current and future.

Despite the enhanced knowledge of the pathophysiology of heart failure (HF), it still remains a serious syndrome with substantial morbidity, mortality, and frequent hospitalizations. These are due to the current improvements in other cardiovascular diseases (like myocardial infarction), the aging population, and growing prevalence of comorbidities. Biomarker-guided management has brought a new dimension in prognostication, diagnosis, and therapy options. Following the recommendation of natriuretic peptides (B-type natriuretic peptide and N-terminal-proBNP), many other biomarkers have been thoroughly studied to reflect different pathophysiological processes (such as fibrosis, inflammation, myocardial injury, and remodeling) in HF and some of them (like cardiac troponins, soluble suppression of tumorigenesis-2, and galectin 3) have subsequently been recommended to aid in the diagnosis and prognostication in HF. Consequently, multi-marker approach has also been approved owing to the varied nature of HF syndrome. In this review, we discussed the guidelines available for HF biomarkers, procedures for evaluating novel markers, and the utilities of both emerging and established biomarkers for risk stratification, diagnosis, and management of HF in the clinics. We later looked at how the rapidly emerging field-OMICs, can help transform HF biomarkers discoveries and establishment.