Scleraxis and fibrosis in the pressure-overloaded heart.

Aims: In response to pro-fibrotic signals, scleraxis regulates cardiac fibroblast activation in vitro via transcriptional control of key fibrosis genes such as collagen and fibronectin; however, its role in vivo is unknown. The present study assessed the impact of scleraxis loss on fibroblast activation, cardiac fibrosis, and dysfunction in pressure overload-induced heart failure.

Methods And Results: Scleraxis expression was upregulated in the hearts of non-ischemic dilated cardiomyopathy patients, and in mice subjected to pressure overload by transverse aortic constriction (TAC).

Regulation of Cardiac Fibroblast GLS1 Expression by Scleraxis.

Fibrosis is an energy-intensive process requiring the activation of fibroblasts to myofibroblasts, resulting in the increased synthesis of extracellular matrix proteins. Little is known about the transcriptional control of energy metabolism in cardiac fibroblast activation, but glutaminolysis has been implicated in liver and lung fibrosis. Here we explored how pro-fibrotic TGFβ and its effector scleraxis, which drive cardiac fibroblast activation, regulate genes involved in glutaminolysis, particularly the rate-limiting enzyme glutaminase (GLS1).

Sirtuin 3 overexpression preserves maximal sarco(endo)plasmic reticulum calcium ATPase activity in the skeletal muscle of mice subjected to high fat - high sucrose feeding.

Sarco(endo)plasmic reticulum calcium (Ca) ATPase (SERCA) transports Ca in muscle. Impaired SERCA activity may contribute to diabetic myopathy. Sirtuin (SIRT) 3 regulates muscle metabolism and function; however, it is unknown if SIRT3 regulates muscle SERCA activity or acetylation.

Muscle-specific sirtuin 3 overexpression does not attenuate the pathological effects of high-fat/high-sucrose feeding but does enhance cardiac SERCA2a activity.

Obesity, type 2 diabetes, and heart disease are linked to an unhealthy diet. Sarco(endo)plasmic reticulum calcium (Ca ) ATPase 2a (SERCA2a) controls cardiac function by transporting Ca in cardiomyocytes. SERCA2a is altered by diet and acetylation, independently; however, it is unknown if diet alters cardiac SERCA2a acetylation.

Frailty status and cardiovascular disease risk profile in middle-aged and older females.

Objective: Frailty and pre-frailty are known to increase the risk of developing cardiovascular disease (CVD). However, the risk profiles of females are not well characterized. The aim of this study is to characterize the CVD risk profiles of robust, pre-frail and frail females.

Myokines as biomarkers of frailty and cardiovascular disease risk in females.

Frailty is a risk factor for cardiovascular disease (CVD). Biomarkers have the potential to detect the early stages of frailty, such as pre-frailty. Myokines may act as biomarkers of frailty-related disease progression, as a decline in muscle health is a hallmark of the frailty phenotype.

Exercise-induced increases in the expression and activity of cardiac sarcoplasmic reticulum calcium ATPase 2 is attenuated in AMPKα kinase-dead mice.

Exercise enhances cardiac sarcoplasmic reticulum Ca-ATPase 2a (SERCA2a) function through unknown mechanisms. The present study tested the hypothesis that the positive effects of exercise on SERCA2a expression and function in the left ventricle is dependent on adenosine-monophosphate-activated protein kinase (AMPK) α2 function. AMPKα kinase-dead (KD) transgenic mice, which overexpress inactivated AMPKα subunit, and wild-type C57Bl/6 (WT) mice were randomized into sedentary groups or groups with access to running wheels.

Standardization of the Fried frailty phenotype improves cardiovascular disease risk discrimination.

Background: Standardizing the Fried criteria (S-FC) using cutoffs specific to the patient population improves adverse outcome prediction. However, there is limited evidence to determine if a S-FC assessment can improve discrimination of cardiovascular disease (CVD) risk in middle-aged and older women.

Design: The objective of this cross-sectional analysis was to compare the ability of the Fried frailty phenotype criteria (FC) to discriminate between individuals at higher risk for CVD according to the Framingham Risk Score and Rasmussen Disease Score in comparison to the S-FC.

Exercise-induced irisin release as a determinant of the metabolic response to exercise training in obese youth: the EXIT trial.

The mechanisms underlying the metabolic improvements following aerobic exercise training remain poorly understood. The primary aim of this study was to determine if an adipomyokine, irisin, responded to acute exercise was associated with the metabolic adaptations to chronic aerobic exercise in obese youth. The acute response to exercise was assessed in 11 obese youth following 45-min acute bouts of aerobic (AE) and resistance exercise (RE).

Protocol for the HAPPY Hearts study: cardiovascular screening for the early detection of future adverse cardiovascular outcomes in middle-aged and older women: a prospective, observational cohort study.

Introduction: Efforts to identify individuals at a higher risk for adverse cardiovascular outcomes focus on traditional risk factors, such as age, sex, smoking status, blood pressure and and cholesterol; however, this approach does not directly assess cardiovascular function and may underestimate the risk of experiencing adverse cardiovascular outcomes in women. This prospective, observational cohort study will examine the ability of the Heart Attack Prevention Program for You (HAPPY) Hearts screening protocol, a series of non-invasive procedures to identify middle-aged and older women who are at an elevated risk for experiencing an adverse cardiovascular event in the 5-year period after screening. The predictive value of the HAPPY Hearts protocol will also be compared with the Framingham Risk Score to determine the sensitivity for estimating risk for an adverse cardiovascular outcome.

Differential regulation of the fiber type-specific gene expression of the sarcoplasmic reticulum calcium-ATPase isoforms induced by exercise training.

The regulatory role of adenosine monophosphate-activated protein kinase (AMPK)-α2 on sarcoplasmic reticulum calcium-ATPase (SERCA) 1a and SERCA2a in different skeletal muscle fiber types has yet to be elucidated. Sedentary (Sed) or exercise-trained (Ex) wild-type (WT) and AMPKα2-kinase dead (KD) transgenic mice, which overexpress a mutated and inactivated AMPKα2 subunit, were utilized to characterize how genotype or exercise training influenced the regulation of SERCA isoforms in gastrocnemius. As expected, both Sed and Ex KD mice had >40% lower AMPK phosphorylation and 30% lower SERCA1a protein than WT mice (P < 0.