Advances in miR-132-Based Biomarker and Therapeutic Potential in the Cardiovascular System

Atherosclerotic cardiovascular disease and subsequent heart failure threaten global health and impose a huge economic burden on society. MicroRNA-132 (miR-132), a regulatory RNA ubiquitously expressed in the cardiovascular system, is up-or down-regulated in the plasma under various cardiac conditions and may serve as a potential diagnostic or prognostic biomarker. More importantly, miR-132 in the myocardium has been demonstrated to be a master regulator in many pathological processes of ischemic or nonischemic heart failure in the past decade, such as myocardial hypertrophy, fibrosis, apoptosis, angiogenesis, calcium handling, neuroendocrine activation, and oxidative stress, through downregulating target mRNA expression. Preclinical and clinical phase 1b studies have suggested antisense oligonucleotide targeting miR-132 may be a potential therapeutic approach for ischemic or nonischemic heart failure in the future. This review aims to summarize recent advances in the physiological and pathological functions of miR-132 and its possible diagnostic and therapeutic potential in cardiovascular disease.

Neuroendocrine and Cardiovascular Activation During Aggressive Reactivity in Dogs

Our aim was to investigate cardiovascular activation by measuring changes in facial and body surface temperature using infrared thermography, and neuroendocrine activation using salivary cortisol (CORT) and serotonin concentration (SER) in dogs exhibiting aggressive reactivity in real time. Based on two factors, owner-reported past aggressive behaviors, and detailed behavioral observations collected during a Socially Acceptable Behavior test consisting of 16 subtests and, each individual was categorized as aggressive or non-aggressive. CORT and SER showed no difference in neuroendocrine activity between dogs, but aggressive dogs with higher levels of aggression were found to have lower SER. Aggressive dogs also had an increase in facial temperature from pre-test values. The discovery of a correlation between tail wagging and left tail wagging with aggression level and aggression-related behaviors in aggressive dogs is further evidence of the right hemisphere specialization for aggression previously reported in the literature. This study provides the first evidence that both cardiovascular and neuroendocrine systems are activated during an active act of aggression in dogs.

Susceptibility Variations in Air Pollution Health Effects: Incorporating Neuroendocrine Activation

Diverse host factors/phenotypes may exacerbate or diminish biological responses induced by air pollutant exposure. We lack an understanding of biological indicators of environmental exposures that culminate in a physiological response versus those that lead to adversity. Variations in response phenotype might arise centrally and/or at the local tissue level. In addition to genetic differences, the current evidence supports the roles of preexisting cardiopulmonary diseases, diabetes, diet, adverse prenatal environments, neurobehavioral disorders, childhood infections, microbiome, sex, and psychosocial stressors in modifying the susceptibility to air pollutant exposures. Animal models of human diseases, obesity, nutritional inadequacies, and neurobehavioral conditions have been compared with healthy controls to understand the causes of variations in susceptibility. Although psychosocial stressors have been associated with increased susceptibility to air pollutant effects, the contribution of neuroendocrine stress pathways in mediating these effects is just emerging. The new findings of neuroendocrine activation leading to systemic metabolic and immunological effects of air pollutants, and the potential contribution to allostatic load, emphasize the consideration of these mechanisms into susceptibility. Variations in susceptibility to air pollution health effects are likely to underlie host genetic and physiological conditions in concert with disrupted neuroendocrine circuitry that alters physiological stability under the influence of stressors.

Atrial and Brain Natriuretic Peptides- Benefits and Limits of their use in Cardiovascular Diseases

Natriuretic peptides, produced by cardiac myocytes, are regulators of the intravascular volume and blood pressure, and also exhibit neuroendocrine, metabolic and growth controlling effects. In heart failure, their synthesis increases exponentially as part of the neuroendocrine activation, but their beneficial effects are diminished. The paper reviews relevant data about their role as diagnosis and prognosis markers in heart failure, the hemodynamic and clinical benefits of their use as therapy in heart failure, together with the main adverse effects. Peptides non-specifically increase in extracardiac pathology and the literature reveals the mechanisms of increase, significance and threshold values to exclude cardiac dysfunction.

Cardiovascular biomarkers predict fragility fractures in older adults

ObjectiveTo assess the role of four biomarkers of neuroendocrine activation and endothelial dysfunction in the longitudinal prediction of fragility fractures.MethodsWe analysed a population-based prospective cohort of 5415 community-dwelling individuals (mean age, 68.9±6.2 years) enrolled in the Malmö Preventive Project followed during 8.1±2.9 years, and investigated the longitudinal association between C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1 precursor fragment (CT-proET-1), the mid-regional fragments of pro-adrenomedullin (MR-proADM) and pro-atrial natriuretic peptide (MR-proANP), and incident vertebral, pelvic and extremity fractures.ResultsOverall, 1030 (19.0%) individuals suffered vertebral, pelvic or extremity fracture. They were older (70.7±5.8 vs 68.4±6.3 years), more likely women (46.9% vs 26.3%), had lower body mass index and diastolic blood pressure, were more often on antihypertensive treatment (44.1% vs 38.4%) and had more frequently history of fracture (16.3% vs 8.1%). Higher levels of MR-proADM (adjusted HR (aHR) per 1 SD: 1.51, 95% CI 1.01 to 2.28, p<0.001) and MR-proANP (aHR: 1.23, 95% CI 1.05 to 1.45, p<0.001) were independently associated with increased risk of any fracture. The fracture risk increased linearly across MR-proANP quartiles. Individuals who were in the top quartile of all four biomarkers had a significant higher risk of fracture at any site (aHR: 2.32, 95% CI 1.86 to 2.91), vertebral fracture (aHR: 3.16, 95% CI 1.97 to 5.07) and femoral fracture (aHR: 2.35, 95% CI 1.64 to 3.36).ConclusionsElevated levels of MR-proADM and MR-proANP independently predict fragility fractures in older adults. In subjects with top quartile levels of all four biomarkers there is a twofold to threefold increase in risk of vertebral and femoral fractures.