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Heart failure with preserved ejection fraction (HFpEF) is an essential subtype of heart failure accounting for 40% of the total. However, the related pathological mechanism and drug therapy research have been stagnant for a long time. The direct cause of this dilemma is the heterogeneity of HFpEF. And some researchers believe that there is no common pathway to reach the origin of HFpEF; others argue that there is an unidentified unified pathophysiological process hidden beneath the ice surface. Aside from the debate, a series of clinical studies have shown that hypertension and obesity play a fundamental role in the pathogenesis of HFpEF. These results imply that there may be two parallel pathological processes interweaved in one disease, manifested as multiple coexistent pathological phenomena, like a shadow. Meanwhile, the prevalence of HFpEF in women is higher than in men in any given age group, especially prominent in elderly patients. These pathological processes and epidemiological data reflect gender differences, reminding us to shift our attention to estrogen. This article will review the parallel pathogenesis of HFpEF, and also introduce sex differences and the potential effect of estrogen in this condition below., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Calcium ion (Ca 2+ ) cycle plays a crucial role in the contraction and relaxation of cardiomyocytes. The sarcoplasmic reticulum (SR) acts as an organelle for storing Ca 2+ , which mediated the release and re-uptake of Ca 2+ during contraction and relaxation. Disorders of SR function lead to the dysfunction of Ca 2+ cycle and myocardial cell function. The sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase 2a (SERCA2a) acts as a subtype of SERCA expressed in the heart, which mediates the contraction of cardiomyocytes and Ca 2+ in the cytoplasm to re-enter into the SR. The rate of uptake of Ca 2+ by the SR determines the rate of myocardial relaxation. The regulation of SERCA2a activity controls the contractility and relaxation of the heart, affecting cardiac function. The expression and activity of SERCA2a are reduced in failing hearts. Gene therapy by increasing the expression of SERCA2a in the heart has been proven effective. In addition, SERCA2a is regulated by a variety of factors, including transmembrane micropeptides, protein kinases, and post-translational modifications (PTMs). In this review, we discuss the regulatory factors of SERCA2a and provide new insights into future treatments and the direction of heart failure research. In addition, gene therapy for SERCA2a has recently emerged as therapeutic option and hence will be discussed in this review.

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.

As a chronic inflammatory disease, atherosclerosis is characterized by accumulation of lipid-rich macrophages on the inner walls of arteries. Deposited macrophages promote atherosclerotic lesion progression; therefore they are viewed as the main targets in order to alleviate atherosclerosis. Danlou tablet, a patented Chinese Medicine, has long been used to treat cardiovascular diseases. In the present study, we used Apolipoprotein E-deficient (ApoE -/- ) mice model and in vitro cell line of RAW264.7 to explore the mechanisms of ethanol extracts of Danlou tablet (EEDT) in treating atherosclerosis. The potential targets that EEDT works to treat atherosclerosis were predicted by "Network pharmacology analysis", based on which we designed mRNA array of 93 genes. Then mRNA array and oil red O staining were performed in aortic extracted from the cohorts of Control (C57BL/6 mice, chow fed), Model (ApoE -/- C57BL/6 mice, 20 weeks of high-fat diet) and EEDT intervening (ApoE -/- mice, 20 weeks of high-fat diet with 12 weeks of EEDT treatment) group. Furthermore, mRNA array, inflammation cytokines and lipid content were examined in RAW264.7 cell line. It was showed that EEDT decreased the expressions of inflammation cytokines by down regulating NF-κB singling pathway and accelerated cholesterol effluent through activating PPARα/ABCA1 signaling pathway. On the other hand, activation of NF-κB pathway or suppression of PPARα/ABCA1 signaling pathway both abolished the therapeutic effect of EEDT. In conclusion, EEDT played a key role in anti-inflammation and preventing lipid deposition in macrophages of atherosclerosis via suppressing NF-κB signaling and triggering PPARα/ABCA1 signaling pathway., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

An increasing number of diseases are being newly closely associated with inflammation, where microRNAs seem to play a critical role in the whole disease process from initiation to development. MicroRNAs are small non-coding RNAs that govern gene expression and modulation by means of mRNA degradation or translational repression. After several profound research studies, new correlations between microRNA-155 and inflammation-related diseases are strongly emerging. Hence, we review in this paper the possible molecular mechanisms of microRNA-155 in inflammatory disorders. Furthermore, we also consider the feasibility of targeting it as a bright alternative to improve the early diagnose statistics and treatments in those diseases. MicroRNA-155 features a novel breakthrough in fine-tuning inflammatory responses and, thereby, in treating a wide spectrum of diseases with inflammation as a common denominator.