The development of cardiovascular pathologies is partly attributed to epigenetic causes, including histone methylation, which appears to be an important marker in hearts that develop cardiac hypertrophy. Previous studies showed that the histone demethylase JMJD2A can regulate the hypertrophic process in murine cardiomyocytes. However, the influence of JMJD2A on cardiac hypertrophy in a human cardiomyocyte model is still poorly understood. In the present study, cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) were used. Hypertrophy was induced by angiotensin II and endothelin-1 (ET-1), and transfections were performed to overexpress JMJD2A and for small interfering RNA (siRNA)-induced silencing of JMJD2A. Gene expression analyses were determined using RT-PCR and Western blot. The expression levels of B-type natriuretic peptide (BNP), natriuretic peptide A (ANP), and beta myosin heavy chain (β-MHC) were increased by nearly 2–10-fold with ET-1 compared with the control. However, a higher level of JMJD2A and UTX was detected, whereas the level of JMJD2C was lower. When cardiomyocytes were transiently transfected with JMJD2A, an increase close to 150% in BNP was observed, and this increase was greater after treatment with ET-1. To verify the specificity of JMJD2A activity, a knockdown was performed by means of siRNA-JMJD2A, which led to a significant reduction in BNP. The involvement of JMJD2A suggests that histone-specific modifications are associated with genes encoding proteins that are actively transcribed during the hypertrophy process. Since BNP is closely related to JMJD2A expression, we suggest that there could be a direct influence of JMJD2A on the expression of BNP. These results may be studied further to reduce cardiac hypertrophy via the regulation of epigenetic modifiers.

Epigenetic changes induced by histone demethylases play an important role in differentiation and pathological changes in cardiac cells. However, the role of the jumonji family of demethylases in the development of cardiac hypertrophy remains elusive. In this study, the presence of different histone demethylases in cardiac cells was evaluated after hypertrophy was induced with neurohormones. A cell line from rat cardiomyocytes was used as a biological model. The phenotypic profiles of the cells, as well as the expression of histone demethylases, were studied through immunofluorescence, transient transfection, western blot, and qRT-PCR analysis after inducing hypertrophy by angiotensin II and endothelin-1. An increase in fetal gene expression (ANP, BNP, andβ-MHC) was observed in cardiomyocytes after treatment with angiotensin II and endothelin-1. A significant increase in JMJD2A expression, but not in UTX or JMJD2C expression, was observed. When JMJD2A was overexpressed in cardiomyocytes through transient transfection, the effect of neurohormones on fetal cardiac gene expression was increased. We conclude that JMJD2A plays a principal role in the regulation of fetal cardiac genes, which increase in expression during the pathological hypertrophic process.

Mesenchymal stem cells are a diverse population of cells with a wide range of potential therapeutic applications. In particular, cells from adipose tissue have the distinction of being easily accessible and contain a lot of stem cells. ADMSCs can be induced to mature adipocyte and activate the energy expenditure upon treatment with total PPARγagonists. Additionally these cells may respond to cold by activating the thermogenic program. In the present study, we determined the effect of partial agonism of PPARγand temperature reduction on phenotype and metabolic activity of ADMSCs from human adipose subcutaneous tissue. We found that adipocytes differentiated with total and partial agonists of PPARγand exposed to 31°C are able to respond to cold significantly increasing the expression of thermogenic proteins such as UCP1, PGC1α, and CITED1, a marker of beige phenotype. Additionally, we found that adipocyte cells subjected to cold had a reduction in triglycerides and increased adiponectin levels. These data confirm the promising role of ADMSCs as a treatment for metabolic disorders since it is possible to induce them to mature adipocytes and modulate their phenotype toward a cell with high-energy expenditure and metabolic beneficial effect.

Increasing thermogenesis in white adipose tissues can be used to treat individuals at high risk for obesity and cardiovascular disease. The objective of this study was to determine the function of EP300-interacting inhibitor of differentiation (EID1), an inhibitor of muscle differentiation, in the induction of beige adipocytes from adipose mesenchymal stem cells (ADMSCs). Subcutaneous adipose tissue was obtained from healthy women undergoing abdominoplasty. ADMSCs were isolated in vitro, grown, and transfected with EID1 or EID1 siRNA, and differentiation was induced after 48 h by administering rosiglitazone. The effects of EID1 expression under the control of the aP2 promoter (aP2-EID1) were also evaluated in mature adipocytes that were differentiated from ADMSCs. Transfection of EID1 into ADMSCs reduced triglyceride accumulation while increasing levels of thermogenic proteins, such as PGC1α, TFAM, and mitochondrial uncoupling protein 1 (UCP1), all of which are markers of energy expenditure and mitochondrial activity. Furthermore, increased expression of the beige phenotype markers CITED1 and CD137 was observed. Transfection of aP2-EID1 transfection induced the conversion of mature white adipocytes to beige adipocytes, as evidenced by increased expression of PGC1α, UCP1, TFAM, and CITED1. These results indicate that EID1 can modulate ADMSCs, inducing a brown/beige lineage. EID1 may also activate beiging in white adipocytes obtained from subcutaneous human adipose tissue.

Currently, cardiovascular diseases are a major contributor to morbidity and mortality worldwide, having a significant negative impact on both the economy and public health. The renin–angiotensin system contributes to a high spectrum of cardiovascular disorders and is essential for maintaining normal cardiovascular homeostasis. Overactivation of the classical renin–angiotensin system is one of the most important pathophysiological mechanisms in the progression of cardiovascular diseases. The counter-regulatory renin–angiotensin system is an alternate pathway which favors the synthesis of different peptides, including Angiotensin-(1-7), Angiotensin-(1-9), and Alamandine. These peptides, via the angiotensin type 2 receptor (AT2R), MasR, and MrgD, initiate multiple downstream signaling pathways that culminate in the activation of various cardioprotective mechanisms, such as decreased cardiac fibrosis, decreased myocardial hypertrophy, vasodilation, decreased blood pressure, natriuresis, and nitric oxide synthesis. These cardioprotective effects position them as therapeutic alternatives for reducing the progression of cardiovascular diseases. This review aims to show the latest findings on the cardioprotective effects of the main peptides of the counter-regulatory renin–angiotensin system.

: Quorum-sensing is a communication mechanism between bacteria with the ability to activate signaling pathways in the bacterium and in the host cells. Pseudomonas aeruginosa is a pathogen with high clinical relevance due to its vast virulence factors repertory and wide antibiotic resistance mechanisms. Due to this, it has become a pathogen of interest for developing new antimicrobial agents in recent years. P. aeruginosa has three major QS systems that regulate a wide gene range linked with virulence factors, metabolic regulation, and environment adaption. Consequently, inhibiting this communication mechanism would be a strategy to prevent the pathologic progression of the infections caused by this bacterium. In this review, we aim to overview the current studies about the signaling mechanisms of the QS system of P. aeruginosa and its effects on this bacterium and the host.