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Biology subjects

Ziolo, M. T.

Publications and source records attributed to Ziolo, M. T..

2 recordsLinked to original sources

Old mice have a functionally distinct contractile reserve from obese mice

BackgroundCardiovascular disease (CVD) is the leading cause of global mortality, with recent increases attributed to demographic shifts in age and rising rates of obesity. Diminished contractile reserve is a hallmark of a diseased heart; assessing contractile reserve is pivotal in prognosticating and monitoring CVD progression. The Frank-Starling mechanism and sympathetic stimulation are key to enhance contractile reserve but have not been explored in vivo in old and obese mouse models of CVD. This project aims to use speckle tracking echocardiography (STE) to characterize the function of the heart at baseline, with increased preload, and with sympathetic stimulation. We hypothesize that along with blunted systolic function, diastolic function, and contractility, old and obese mice will have a blunted contractile reserve. MethodsSTE was obtained for control (4- month-old), aged (24-month-old), and obese mice (high fat diet-induced). Mice received an intravenous injection of 150L saline to increase preload to assess the Frank-Starling response, followed by injection of {beta}1adrenergic receptor agonist dobutamine to assess sympathetic response. ResultsAt baseline, aging and obese mice demonstrated blunted systolic, diastolic function, and contractility. Endocardial and epicardial wall displacement differed between aging and obese mice with contractile reserve, indicating that they have functionally distinct cardiac phenotypes. ConclusionsThis study is the first to demonstrate blunted systolic function, diastolic function, and contractility through STE in aging and obese mice. Our novel method for investigating the contractile reserve of mice demonstrated aging and obese mice have dissimilar responses when assessing contractile reserve, which could contribute to their distinct functional phenotypes.

physiology↗

Consequences of PDGFRα+ fibroblast reduction in adult murine hearts

Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. Although fibrosis accompanies many cardiac pathologies and is generally deleterious, the role of fibroblasts in maintaining the basal ECM network and in fibrosis in vivo is poorly understood. We genetically ablated fibroblasts in mice to evaluate the impact on homeostasis of adult ECM and cardiac function after injury. Fibroblast-ablated mice demonstrated a 60-80% reduction in cardiac fibroblasts, which did not overtly alter fibrillar collagen or the ECM proteome evaluated by quantitative mass spectrometry and N-terminomics. However, the distribution and quantity of collagen VI, a microfibrillar collagen that forms an open network with the basement membrane, was altered. In fibroblast-ablated mice, cardiac function was better preserved following angiotensin II/phenylephrine (AngII/PE)-induced fibrosis and myocardial infarction. Analysis of cardiomyocyte function demonstrated weaker contractions and slowed calcium decline in both uninjured and AngII/PE infused fibroblast-ablated mice. Moreover, fibroblast-ablated hearts had a similar gene expression profile to hearts with physiological hypertrophy after AngII/PE infusion. Our results indicate that the adult mouse heart tolerated a significant degree of fibroblast loss with potential beneficial impacts on cardiac function. Controlled fibroblast reduction may have therapeutic value in heart disease by providing cardioprotective effects.

cell biology↗