Review

Authors: Guanghong Jia, Michael A Hill, James R Sowers...

Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy. The prevalence of diabetic cardiomyopathy is increasing in parallel with the increase in diabetes mellitus. Diabetic cardiomyopathy is initially characterized by myocardial fibrosis, dysfunctional remodeling, and associated diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure. Impaired cardiac insulin metabolic signaling, mitochondrial dysfunction, increases in oxidative stress, reduced nitric oxide bioavailability, elevations in advanced glycation end products and collagen-based cardiomyocyte and extracellular matrix stiffness, impaired mitochondrial and cardiomyocyte calcium handling, inflammation, renin-angiotensin-aldosterone system activation, cardiac autonomic neuropathy, endoplasmic reticulum stress, microvascular dysfunction, and a myriad of cardiac metabolic abnormalities have all been implicated in the development and progression of diabetic cardiomyopathy. Molecular mechanisms linked to the underlying pathophysiological changes include abnormalities in AMP-activated protein kinase, peroxisome proliferator-activated receptors, O-linked N-acetylglucosamine, protein kinase C, microRNA, and exosome pathways. The aim of this review is to provide a contemporary view of these instigators of diabetic cardiomyopathy, as well as mechanistically based strategies for the prevention and treatment of diabetic cardiomyopathy.

Topics: Animals; Diabetic Cardiomyopathies; Humans; Insulin; Myocardium; Signal Transduction

PubMed: 29449364
DOI: 10.1161/CIRCRESAHA.117.311586

Review

Authors: Anna Picca, Robert T Mankowski, Jonathon L Burman...

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Advancing age is a major risk factor for developing cardiovascular disease because of the lifelong exposure to cardiovascular risk factors and specific alterations affecting the heart and the vasculature during ageing. Indeed, the ageing heart is characterized by structural and functional changes that are caused by alterations in fundamental cardiomyocyte functions. In particular, the myocardium is heavily dependent on mitochondrial oxidative metabolism and is especially susceptible to mitochondrial dysfunction. Indeed, primary alterations in mitochondrial function, which are subsequently amplified by defective quality control mechanisms, are considered to be major contributing factors to cardiac senescence. In this Review, we discuss the mechanisms linking defective mitochondrial quality control mechanisms (that is, proteostasis, biogenesis, dynamics, and autophagy) to organelle dysfunction in the context of cardiac ageing. We also illustrate relevant molecular pathways that might be exploited for the prevention and treatment of age-related heart dysfunction.

Topics: Aging; Animals; Cellular Senescence; Heart; Humans; Mice; Mitochondria; Myocardium; Myocytes, Cardiac; Rats

PubMed: 30042431
DOI: 10.1038/s41569-018-0059-z

Review

Authors: Frederick L Ruberg, John L Berk

Topics: Amyloidosis; Cardiomyopathies; Humans; Myocardium; Prealbumin

PubMed: 22949539
DOI: 10.1161/CIRCULATIONAHA.111.078915

Review

Authors: Eric N Olson

Topics: Humans; Regeneration; Animals; Myocardium; Heart; Myocytes, Cardiac

PubMed: 39074179
DOI: 10.1161/CIRCULATIONAHA.124.070136

Authors: Arvind Bhimaraj, James B Young

Topics: Humans; Recovery of Function; Treatment Outcome; Myocardium; Ventricular Function, Left

PubMed: 39184163
DOI: 10.14797/mdcvj.1446

Review

Authors: Ahmed U Fayyaz, Muhammad Eltony, Larry J Prokop...

Heart failure with preserved ejection fraction (HFpEF) is a major, worldwide health-care problem. Few therapies for HFpEF exist because the pathophysiology of this condition is poorly defined and, increasingly, postulated to be diverse. Although perturbations in other organs contribute to the clinical profile in HFpEF, altered cardiac structure, function or both are the primary causes of this heart failure syndrome. Therefore, studying myocardial tissue is fundamental to improve pathophysiological insights and therapeutic discovery in HFpEF. Most studies of myocardial changes in HFpEF have relied on cardiac tissue from animal models without (or with limited) confirmatory studies in human cardiac tissue. Animal models of HFpEF have evolved based on theoretical HFpEF aetiologies, but these models might not reflect the complex pathophysiology of human HFpEF. The focus of this Review is the pathophysiological insights gained from studies of human HFpEF myocardium. We outline the rationale for these studies, the challenges and opportunities in obtaining myocardial tissue from patients with HFpEF and relevant comparator groups, the analytical approaches, the pathophysiological insights gained to date and the remaining knowledge gaps. Our objective is to provide a roadmap for future studies of cardiac tissue from diverse cohorts of patients with HFpEF, coupling discovery biology with measures to account for pathophysiological diversity.

Topics: Humans; Heart Failure; Stroke Volume; Myocardium; Animals; Ventricular Function, Left; Disease Models, Animal

PubMed: 39198624
DOI: 10.1038/s41569-024-01067-1

Authors: Per Lav Madsen, Annemie Stege Bojer, Martin Sørensen...

Overweight and diabetes (DM) result in premature cardiovascular disease. Even if unaccompanied by ischaemic heart disease, DM stiffens the circulation, which may result in heart failure with preserved ejection fraction. Magnetic resonance imaging studies have documented cardiac hypertrophy, myocardial vascular rarefaction, and myocardial fibrosis in patients with type 2 DM. All three phenotypical changes seem noteworthy targets for early intervention. "Diabetic cardiomyopathy" is years underway and hence early detection may be needed to secure adequate treatment of the metabolic syndrome.

Topics: Humans; Stroke Volume; Ventricular Function, Left; Myocardium; Heart Failure; Cardiomyopathies; Diabetes Mellitus; Magnetic Resonance Imaging

PubMed: 36305260
DOI: No ID Found

Authors: Masato Kanda, Toshio Nagai

Topics: DNA-Binding Proteins; Fibroblasts; Fibrosis; Humans; Mitochondrial Proteins; Myocardium; Signal Transduction

PubMed: 30487381
DOI: 10.1536/ihj.18-530

Review

Authors: Barbara Garmy-Susini, Nathalie Pizzinat, Nicole Villeneuve...

The lymphatic system is a network of vessels and lymphoid tissues that maintain tissue fluid homeostasis, transport intestinal fat, and regulate immune surveillance. Despite a large body of evidence showing the importance of lymphatic vessels in cardiovascular diseases, the role of cardiac lymphatics has not been extensively investigated. This review highlights the chronology of key discoveries in cardiac lymphatic development and function. In physiology, the cardiac lymphatic system dynamically regulates interstitial fluid drainage to the mediastinal lymph nodes to maintain homeostasis and prevent edema. After myocardial infarction, lymphatic vessels in the ischemic heart become dysfunctional and contribute to the development of chronic myocardial edema that aggravates cardiac fibrosis and dysfunction. Stimulation of cardiac lymphangiogenesis, based on the delivery of lymphangiogenic growth factors, such as VEGF-C, may represent a novel therapeutic strategy to improve cardiac function.

Topics: Animals; Extracellular Fluid; Heart; Homeostasis; Humans; Lymphangiogenesis; Lymphatic Vessels; Myocardium

PubMed: 28945567
DOI: 10.1051/medsci/20173308022

Review

Authors: Petra Kleinbongard, Samuel E Senyo, Merry L Lindsey...

Cardiac fibroblasts play a pivotal role in maintaining heart homeostasis by depositing extracellular matrix (ECM) to provide structural support for the myocardium, vasculature, and neuronal network and by contributing to essential physiological processes. In response to injury such as myocardial infarction or pressure overload, fibroblasts become activated, leading to increased ECM production that can ultimately drive left ventricular remodeling and progress to heart failure. Recently, the issued a call for papers on cardiac fibroblasts that yielded articles with topics spanning fibroblast physiology, technical considerations, signaling pathways, and interactions with other cell types. This mini-review summarizes those articles and places the new findings in the context of what is currently known for cardiac fibroblasts and what future directions remain.

Topics: Humans; Animals; Fibroblasts; Myocardium; Extracellular Matrix; Signal Transduction; Ventricular Remodeling

PubMed: 39093000
DOI: 10.1152/ajpheart.00478.2024