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Hemodynamic overload induces pathological cardiac hypertrophy, which is an independent risk factor for intractable heart failure in long run. Beyond neurohumoral regulation, mechanotransduction has been recently recognized as a major regulator of cardiac hypertrophy under a myriad of conditions. However, the identification and molecular features of mechanotransducer on cardiomyocytes are largely sparse. For the first time, we identified Piezo1 (Piezo type mechanosensitive ion channel component 1), a novel mechanosensitive ion channel with preference to Ca 2+ was remarkably upregulated under pressure overload and enriched near T-tubule and intercalated disc of cardiomyocyte. By applying cardiac conditional Piezo1 knockout mice (Piezo1 fl/fl Myh6Cre+, Piezo1 Cko ) undergoing transverse aortic constriction, we demonstrated that Piezo1 was required for the development of cardiac hypertrophy and subsequent adverse remodeling. Activation of Piezo1 by external mechanical stretch or agonist Yoda1 lead to the enlargement of cardiomyocytes in vitro, which was blocked by Piezo1 silencing or Yoda1 analog Dooku1 or Piezo1 inhibitor GsMTx4. Mechanistically, Piezo1 perturbed calcium homeostasis, mediating extracellular Ca 2+ influx and intracellular Ca 2+ overload, thereby increased the activation of Ca 2+ -dependent signaling, calcineurin, and calpain. Inhibition of calcineurin or calpain could abolished Yoda1 induced upregulation of hypertrophy markers and the hypertrophic growth of cardiomyocytes in vitro. From a comprehensive view of the cardiac transcriptome, most of Piezo1 affected genes were highly enriched in muscle cell physiology, tight junction, and corresponding signaling. This study characterizes an undefined role of Piezo1 in pressure overload induced cardiac hypertrophy. It may partially decipher the differential role of calcium under pathophysiological condition, implying a promising therapeutic target for cardiac dysfunction.

Cardiovascular calcification, a kind of ectopic mineralization in cardiovascular system, including atherosclerotic calcification, arterial medial calcification, valve calcification and the gradually recognized heart muscle calcification, is a complex pathophysiological process correlated with poor prognosis. Although several cell types such as smooth muscle cells have been proven critical in vascular calcification, the aetiology of cardiovascular calcification remains to be clarified due to the diversity of cellular origin. Fibroblasts, which possess remarkable phenotypic plasticity that allows rapid adaption to fluctuating environment cues, have been demonstrated to play important roles in calcification of vasculature, valve and heart though our knowledge of the mechanisms controlling fibroblast phenotypic switching in the calcified process is far from complete. Indeed, the lack of definitive fibroblast lineage‐tracing studies and typical expression markers of fibroblasts raise major concerns regarding the contributions of fibroblasts during all the stages of cardiovascular calcification. The goal of this review was to rigorously summarize the current knowledge regarding possible phenotypes exhibited by fibroblasts within calcified cardiovascular system and evaluate the potential therapeutic targets that may control the phenotypic transition of fibroblasts in cardiovascular calcification.

Glutamine is a major energy source for rapidly dividing cells, such as hematopoietic stem cells and cancer cells. Reliance on glutamine is therefore regarded as a metabolic hallmark of proliferating cells. Moreover, reprogramming glutamine metabolism by various factors, including tissue type, microenvironment, pro-oncogenes, and tumor suppressor genes, can facilitate stem cell fate decisions, tumor recurrence, and drug resistance. However, the significance of glutamine metabolism in cardiomyocytes, an end-differentiated cell type, is not fully understood. Existing evidence suggests important roles of glutamine metabolism in the development of cardiovascular diseases. In this review, we have focused on glutaminolysis and its regulatory network in proliferating cells. We have summarized current findings about the role of glutamine utilization in cardiomyocytes and have discussed possibilities of targeting glutamine metabolism for the treatment of cardiovascular diseases.

Dopamine receptor 1 (Dop1) mediates locust attraction behaviors, however, the mechanism by which Dop1 modulates this process remains unknown to date. Here, we identify differentially expressed small RNAs associated with locust olfactory attraction after activating and inhibiting Dop1. Small RNA transcriptome analysis and qPCR validation reveal that Dop1 activation and inhibition downregulates and upregulates microRNA-9a (miR-9a) expression, respectively. miR-9a knockdown in solitarious locusts increases their attraction to gregarious volatiles, whereas miR-9a overexpression in gregarious locusts reduces olfactory attraction. Moreover, miR-9a directly targets adenylyl cyclase 2 (ac2), causing its downregulation at the mRNA and protein levels. ac2 responds to Dop1 and mediates locust olfactory attraction. Mechanistically, Dop1 inhibits miR-9a expression through inducing the dissociation of La protein from pre-miR-9a and resulting in miR-9a maturation inhibition. Our results reveal a Dop1–miR-9a–AC2 circuit that modulates locust olfactory attraction underlying aggregation. This study suggests that miRNAs act as key messengers in the GPCR signaling., Migratory locusts shift between aggregating together during gregarious phases and living individually during solitary phases. Here, the authors find that the D1-like dopamine receptor regulates the olfactory attraction underlying this behavioral switch via microRNA-9a and adenylyl cyclase.