Effects of aging and type 2 diabetes on cardiac structure and function: Underlying mechanisms.

We characterized long-term changes in cardiac structure and function in a high-fat diet/streptozotocin mouse model of aging and type 2 diabetes mellitus (T2D) and examined how the intersection of both conditions alters plasma metabolomics. We also evaluated the possible roles played by oxidative stress, arginase activity and pro-inflammatory cytokines. C57BL/6 male mice (13-month-old) were used.

(-)-Epicatechin Ameliorates Cardiac Fibrosis in a Female Rat Model of Pre-Heart Failure with Preserved Ejection Fraction.

One of the most abundant flavonoids present in cacao is (-)-epicatechin (Epi) and this flavanol has been linked to the cardiovascular health promoting actions of cocoa products. We previously demonstrated that Epi reduces infarct size in rodent models of ischemia/reperfusion and permanent coronary occlusion. Reduced infarct size was associated with decreased left ventricular (LV) oxidative stress (OS) and indicators of inflammation factors, which foster myocardial fibrosis.

Restorative potential of (-)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue.

We examined in a rat model of Gulf War illness (GWI), the potential of (-)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.

Selective FPR2 Agonism Promotes a Proresolution Macrophage Phenotype and Improves Cardiac Structure-Function Post Myocardial Infarction.

Dysregulated inflammation following myocardial infarction (MI) leads to maladaptive healing and remodeling. The study characterized and evaluated a selective formyl peptide receptor 2 (FPR2) agonist BMS-986235 in cellular assays and in rodents undergoing MI. BMS-986235 activated G proteins and promoted β-arrestin recruitment, enhanced phagocytosis and neutrophil apoptosis, regulated chemotaxis, and stimulated interleukin-10 and monocyte chemoattractant protein-1 gene expression.

Antifibrotic Effects of (-)-Epicatechin on High Glucose Stimulated Cardiac Fibroblasts.

Cardiac fibrosis is one of the hallmarks of a diabetic cardiomyopathy. When activated, cardiac fibroblasts (CFs) increase the production of extracellular matrix proteins. Transforming growth factor (TGF)-1 is known to mediate cardiac fibrosis through the SMAD pathway.

Stimulatory effects of (-)-epicatechin and its enantiomer (+)-epicatechin on mouse frontal cortex neurogenesis markers and short-term memory: proof of concept.

Consumption of (-)-epicatechin (Epi), a cacao flavanol improves cognition. The aim was to compare the effects of (-)-Epi or its stereoisomer (+)-Epi on mouse frontal cortex-dependent short-term working memory and modulators of neurogenesis. Three-month-old male mice (n = 7 per group) were provided by gavage either water (vehicle; Veh), (-)-Epi, at 1 mg kg-1 or (+)-Epi at 0.

Effects of (-)-epicatechin on neuroinflammation and hyperphosphorylation of tau in the hippocampus of aged mice.

Evidence has implicated oxidative stress (OS) and inflammation as drivers of neurodegenerative pathologies. We previously reported on the beneficial effects of (-)-epicatechin (Epi) treatment on aging-induced OS and its capacity to restore modulators of mitochondrial biogenesis in the prefrontal cortex of 26-month-old male mice. In the present study using the same mouse model of aging, we examined the capacity of Epi to mitigate hippocampus OS, inflammation, hyperphosphorylation of tau protein, soluble β-amyloid protein levels, cell survival, memory, anxiety-like behavior levels and systemic inflammation.

Development of muscle atrophy and loss of function in a Gulf-War illness model: underlying mechanisms.

Gulf War illness (GWI) afflicts military personnel who served during the Persian Gulf War and is notable for cognitive deficits, depression, muscle pain, weakness, intolerance to exercise, and fatigue. Suspect causal agents include the chemicals pyridostigmine (PB), permetrim (PM) and N,N-diethyl-m-toluamide (DEET) used as protectants against insects and nerve gases. No pre-clinical studies have explored the effects on skeletal muscle (SkM).

Arginase inhibition by (-)-Epicatechin reverses endothelial cell aging.

Endothelial dysfunction (EnD) occurs with aging and endothelial nitric oxide (NO) production by NO synthase (NOS) can be impaired. Low NO levels have been linked to increased arginase (Ar) activity as Ar competes with NOS for L-arginine. The inhibition of Ar activity can reverse EnD and (-)-epicatechin (Epi) inhibits myocardial Ar activity.

Sex related differences in the pathogenesis of organ fibrosis.

The development of organ fibrosis has garnered rising attention as multiple diseases of increasing and/or high prevalence appear to progress to the chronic stage. Such is the case for heart, kidney, liver, and lung where diseases such as diabetes, idiopathic/autoimmune disorders, and nonalcoholic liver disease appear to notably drive the development of fibrosis. Noteworthy is that the severity of these pathologies is characteristically compounded by aging.

The role of inflammation in driving left ventricular remodeling in a pre-HFpEF model.

The incidence of HFpEF continues to increase and ∼2/3 of the patient population are post-menopausal women. Unfortunately, most studies focus on the use of male animal models of remodeling. In this study, however, using female rats to set a model of pre-HFpEF, we provide insights to possible mechanisms that contribute to HFpEF development in humans that will lead us to a better understanding of the underlying pathophysiology of HFpEF.

Unmasking of oestrogen-dependent changes in left ventricular structure and function in aged female rats: a potential model for pre-heart failure with preserved ejection fraction.

Key Points: Heart failure with preserved ejection fraction (HFpEF) is seen more frequently in older women; risk factors include age, hypertension and excess weight. No female animal models of early stage remodelling (pre-HFpEF) have examined the effects that the convergence of such factors have on cardiac structure and function. In this study, we demonstrate that ageing can lead to the development of mild chamber remodelling, diffuse fibrosis and loss of diastolic function.

Embryonary Mouse Cardiac Fibroblast Isolation.

Mouse cardiac fibroblasts have been widely used as an in vitro model for studying fundamental biological processes and mechanisms underlying cardiac pathologies, as well as identifying potential therapeutic targets. Cardiac FBs are relatively easy to culture in a dish and can be manipulated using molecular and pharmacological tools. Because FBs rapidly decrease cell cycle division and proliferative rate after birth, they are prone to phenotypic changes and senescence in cell culture soon after a few passages.

Spontaneous intracerebral hemorrhage in Mexico: results from a Multicenter Nationwide Hospital-based Registry on Cerebrovascular Disease (RENAMEVASC).

Introduction: Scarce information exists on intracerebral hemorrhage (ICH) in Latin America, and the existent is derived from single-center registries with non-generalizable conclusions. The aim of this study is to describe the frequency, etiology, management and outcome of ICH in Mexico.

Patients And Methods: We studied consecutive patients with ICH pertaining to the National Multicenter Registry on Cerebro-vascular Disease (RENAMEVASC), conducted in 25 centers from 14 states of Mexico.