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Circulation Research Feb 2018Heart 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... (Review)
Review
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 -
Circulation Sep 2012
Review
Topics: Amyloidosis; Cardiomyopathies; Humans; Myocardium; Prealbumin
PubMed: 22949539
DOI: 10.1161/CIRCULATIONAHA.111.078915 -
Nature Reviews. Cardiology Sep 2018Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Advancing age is a major risk factor for developing cardiovascular disease because of... (Review)
Review
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 -
International Journal of Molecular... May 2019Cardiac hypertrophy is an adaptive and compensatory mechanism preserving cardiac output during detrimental stimuli. Nevertheless, long-term stimuli incite chronic... (Review)
Review
Cardiac hypertrophy is an adaptive and compensatory mechanism preserving cardiac output during detrimental stimuli. Nevertheless, long-term stimuli incite chronic hypertrophy and may lead to heart failure. In this review, we analyze the recent literature regarding the role of ERK (extracellular signal-regulated kinase) activity in cardiac hypertrophy. ERK signaling produces beneficial effects during the early phase of chronic pressure overload in response to G protein-coupled receptors (GPCRs) and integrin stimulation. These functions comprise (i) adaptive concentric hypertrophy and (ii) cell death prevention. On the other hand, ERK participates in maladaptive hypertrophy during hypertension and chemotherapy-mediated cardiac side effects. Specific ERK-associated scaffold proteins are implicated in either cardioprotective or detrimental hypertrophic functions. Interestingly, ERK phosphorylated at threonine 188 and activated ERK5 (the big MAPK 1) are associated with pathological forms of hypertrophy. Finally, we examine the connection between ERK activation and hypertrophy in (i) transgenic mice overexpressing constitutively activated RTKs (receptor tyrosine kinases), (ii) animal models with mutated sarcomeric proteins characteristic of inherited hypertrophic cardiomyopathies (HCMs), and (iii) mice reproducing syndromic genetic RASopathies. Overall, the scientific literature suggests that during cardiac hypertrophy, ERK could be a "good" player to be stimulated or a "bad" actor to be mitigated, depending on the pathophysiological context.
Topics: Animals; Cardiomegaly; Humans; MAP Kinase Signaling System; Myocardium
PubMed: 31052420
DOI: 10.3390/ijms20092164 -
International Heart Journal 2018
Topics: DNA-Binding Proteins; Fibroblasts; Fibrosis; Humans; Mitochondrial Proteins; Myocardium; Signal Transduction
PubMed: 30487381
DOI: 10.1536/ihj.18-530 -
Biochimica Et Biophysica Acta.... Jul 2020
Topics: Blood Vessels; Heart; Humans; Myocardium
PubMed: 32169504
DOI: 10.1016/j.bbadis.2020.165766 -
Ugeskrift For Laeger Oct 2022Overweight and diabetes (DM) result in premature cardiovascular disease. Even if unaccompanied by ischaemic heart disease, DM stiffens the circulation, which may result...
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 -
Medecine Sciences : M/S 2017The lymphatic system is a network of vessels and lymphoid tissues that maintain tissue fluid homeostasis, transport intestinal fat, and regulate immune surveillance.... (Review)
Review
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 -
Open Biology Aug 2020Diversity among highly specialized cells underlies the fundamental biology of complex multi-cellular organisms. One of the essential scientific questions in cardiac... (Review)
Review
Diversity among highly specialized cells underlies the fundamental biology of complex multi-cellular organisms. One of the essential scientific questions in cardiac biology has been to define subpopulations within the heart. The heart parenchyma comprises specialized cardiomyocytes (CMs). CMs have been canonically classified into a few phenotypically diverse subpopulations largely based on their function and anatomic localization. However, there is growing evidence that CM subpopulations are in fact numerous, with a diversity of genetic origin and putatively different roles in physiology and pathophysiology. In this chapter, we introduce a recently discovered CM subpopulation: phenylethanolamine--methyl transferase (Pnmt)-derived cardiomyocytes (PdCMs). We discuss: (i) canonical classifications of CM subpopulations; (ii) discovery of PdCMs; (iii) Pnmt and the role of catecholamines in the heart; similarities and dissimilarities of PdCMs and canonical CMs; and (iv) putative functions of PdCMs in both physiological and pathological states and future directions, such as in intra-cardiac adrenergic signalling.
Topics: Age Factors; Animals; Biomarkers; Catecholamines; Cell Plasticity; Electrophysiological Phenomena; Humans; Myocardium; Myocytes, Cardiac; Organogenesis; Phenotype; Phenylethanolamine N-Methyltransferase
PubMed: 32810421
DOI: 10.1098/rsob.200095 -
Circulation Research Sep 2011
Topics: Animals; Cell Differentiation; Humans; MicroRNAs; Mitosis; Myocardium; Myocytes, Cardiac
PubMed: 21885834
DOI: 10.1161/CIRCRESAHA.111.252627