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Right ventricular fibrosis is a stress response, predominantly mediated by cardiac fibroblasts. This cell population is sensitive to increased levels of pro-inflammatory cytokines, pro-fibrotic growth factors and mechanical stimulation. Activation of fibroblasts results in the induction of various molecular signaling pathways, most notably the mitogen-activated protein kinase cassettes, leading to increased synthesis and remodeling of the extracellular matrix. While fibrosis confers structural protection in response to damage induced by ischemia or (pressure and volume) overload, it simultaneously contributes to increased myocardial stiffness and right ventricular dysfunction. Here, we review state-of-the-art knowledge of the development of right ventricular fibrosis in response to pressure overload and provide an overview of all published preclinical and clinical studies in which right ventricular fibrosis was targeted to improve cardiac function.

Purpose To estimate the prevalence of metabolic syndrome (MetS) in the US National Health and Nutrition Examination Survey (NHANES) 2011–18. Methods This study included 8183 eligible nonpregnant participants aged ≥20 years from the NHANES 2011–18. MetS was defined as the presence of at least three of the following components: central obesity, reduced high-density lipoprotein cholesterol, elevated triglycerides, elevated blood pressure, and elevated fasting blood glucose. The prevalence of MetS was estimated taking into account the complex sampling. The time trend was evaluated using logistic regression. Results The total prevalence of MetS increased from 37.6% [95% confidence interval (CI): 34.0%–41.4%] in 2011–12 to 41.8% (95% CI: 38.1%–45.7%) in 2017–18 (P for trend = .028). Among the MetS components, the prevalence of elevated glucose increased from 48.9% (95% CI: 45.7%–52.5%) in 2011–12 to 64.7% (95% CI: 61.4%–67.9%) in 2017–18 (P for trend Conclusion The prevalence of MetS increased during 2011–18, notably in participants with low educational attainment. Lifestyle modification is needed to prevent MetS and the associated risks of diabetes and cardiovascular disease. Key messages What is already known on this topic: Prevalence of metabolic syndrome is an index of the cardiometabolic health of a population. What this study adds: The prevalence of metabolic syndrome in US adults increased during 2011–18, notably in participants with low educational attainment. How this study might affect research, practice, or policy: Lifestyle modification is needed to prevent metabolic syndrome and the associated risks of diabetes and cardiovascular disease.

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AIMS: Research on the pathophysiology of right ventricular (RV) failure has, in spite of the associated high mortality and morbidity, lagged behind compared to the left ventricle (LV).Previous work from our lab revealed that the embryonic basic helix-loop-helix transcription factor heart and neural crest derivatives expressed-2 (Hand2) is re-expressed in the adult heart and activates a 'fetal gene program' contributing to pathological cardiac remodeling under conditions of LV pressure overload. As such, ablation of cardiac expression of Hand2 conferred protection to cardiac stress and abrogated the maladaptive effects that were observed upon increased expression levels. In this study, we aimed to understand the contribution of Hand2 to RV remodeling in response to pressure overload induced by pulmonary artery banding (PAB). METHODS AND RESULTS: In the present study, Hand2F/F and MCM- Hand2F/F mice were treated with tamoxifen (control and knockout, respectively) and subjected to six weeks of RV pressure overload induced by PAB. Echocardiographic- and MRI-derived hemodynamic parameters as well as molecular remodeling were assessed for all experimental groups and compared to sham-operated controls. Six weeks after PAB, levels of Hand2 expression increased in the control banded animals but, as expected, remained absent in the knockout hearts. Despite the dramatic differences in Hand2 expression, pressure overload resulted in impaired cardiac function independently of the genotype. In fact, Hand2 depletion seems to sensitize the RV to pressure overload as these mice develop more hypertrophy and more severe cardiac dysfunction. Higher expression levels of HAND2 were also observed in RV samples of human hearts from patients with pulmonary hypertension. In turn, the LV of RV-pressure overloaded hearts was also dramatically affected as reflected by changes in shape, decreased LV mass and impaired cardiac function. RNA sequencing revealed a distinct set of genes that are dysregulated in the pressure-overloaded RV, compared to the previously described pressure-overloaded LV. CONCLUSIONS: Cardiac-specific depletion of Hand2 is associated with severe cardiac dysfunction in conditions of RV pressure overload. While inhibiting Hand2 expression can prevent cardiac dysfunction in conditions of LV pressure overload, the same does not hold true for conditions of RV pressure overload. This study highlights the need to better understand the molecular mechanisms driving pathological remodeling of the RV in contrast to the LV, in order to better diagnose and treat patients with RV or LV failure. TRANSLATIONAL PERSPECTIVE: RV failure associated with pulmonary hypertension reduces long-term survival rate to 55% within 3 years, suggesting that 3 years after diagnosis almost half of the patients will die. To revert these numbers an adequate RV-specific and, therefore, more efficient treatment is needed. Our work suggests that current therapies and potential mechanisms underlying LV failure may not be suitable for RV failure. While Hand2 deletion is favorable in LV response to stress, it is particularly detrimental in the RV under similar conditions, and thus, highlighting potential severe consequences of not differentiating therapeutic targets or treatment for RV or LV failure.