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The Journal of Clinical Investigation Aug 2021Circadian rhythm evolved to allow organisms to coordinate intrinsic physiological functions in anticipation of recurring environmental changes. The importance of this... (Review)
Review
Circadian rhythm evolved to allow organisms to coordinate intrinsic physiological functions in anticipation of recurring environmental changes. The importance of this coordination is exemplified by the tight temporal control of cardiac metabolism. Levels of metabolites, metabolic flux, and response to nutrients all oscillate in a time-of-day-dependent fashion. While these rhythms are affected by oscillatory behavior (feeding/fasting, wake/sleep) and neurohormonal changes, recent data have unequivocally demonstrated an intrinsic circadian regulation at the tissue and cellular level. The circadian clock - through a network of a core clock, slave clock, and effectors - exerts intricate temporal control of cardiac metabolism, which is also integrated with environmental cues. The combined anticipation and adaptability that the circadian clock enables provide maximum advantage to cardiac function. Disruption of the circadian rhythm, or dyssynchrony, leads to cardiometabolic disorders seen not only in shift workers but in most individuals in modern society. In this Review, we describe current findings on rhythmic cardiac metabolism and discuss the intricate regulation of circadian rhythm and the consequences of rhythm disruption. An in-depth understanding of the circadian biology in cardiac metabolism is critical in translating preclinical findings from nocturnal-animal models as well as in developing novel chronotherapeutic strategies.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Heart Diseases; Humans; Myocardium
PubMed: 34338224
DOI: 10.1172/JCI148276 -
Cells Nov 2021For both the atria and ventricles, fibrosis is generally recognized as one of the key determinants of conduction disturbances. By definition, fibrosis refers to an... (Review)
Review
For both the atria and ventricles, fibrosis is generally recognized as one of the key determinants of conduction disturbances. By definition, fibrosis refers to an increased amount of fibrous tissue. However, fibrosis is not a singular entity. Various forms can be distinguished, that differ in distribution: replacement fibrosis, endomysial and perimysial fibrosis, and perivascular, endocardial, and epicardial fibrosis. These different forms typically result from diverging pathophysiological mechanisms and can have different consequences for conduction. The impact of fibrosis on propagation depends on exactly how the patterns of electrical connections between myocytes are altered. We will therefore first consider the normal patterns of electrical connections and their regional diversity as determinants of propagation. Subsequently, we will summarize current knowledge on how different forms of fibrosis lead to a loss of electrical connectivity in order to explain their effects on propagation and mechanisms of arrhythmogenesis, including ectopy, reentry, and alternans. Finally, we will discuss a histological quantification of fibrosis. Because of the different forms of fibrosis and their diverging effects on electrical propagation, the total amount of fibrosis is a poor indicator for the effect on conduction. Ideally, an assessment of cardiac fibrosis should exclude fibrous tissue that does not affect conduction and differentiate between the various types that do; in this article, we highlight practical solutions for histological analysis that meet these requirements.
Topics: Animals; Confounding Factors, Epidemiologic; Disease Models, Animal; Electrophysiological Phenomena; Fibrosis; Heart Conduction System; Humans; Myocardium
PubMed: 34831442
DOI: 10.3390/cells10113220 -
Cellular Signalling Jan 2021The heart can respond to increased pathophysiological demand through alterations in tissue structure and function . This process, called cardiac remodeling, is... (Review)
Review
The heart can respond to increased pathophysiological demand through alterations in tissue structure and function . This process, called cardiac remodeling, is particularly evident following myocardial infarction (MI), where the blockage of a coronary artery leads to widespread death of cardiac muscle. Following MI, necrotic tissue is replaced with extracellular matrix (ECM), and the remaining viable cardiomyocytes (CMs) undergo hypertrophic growth. ECM deposition and cardiac hypertrophy are thought to represent an adaptive response to increase structural integrity and prevent cardiac rupture. However, sustained ECM deposition leads to the formation of a fibrotic scar that impedes cardiac compliance and can induce lethal arrhythmias. Resident cardiac fibroblasts (CFs) are considered the primary source of ECM molecules such as collagens and fibronectin, particularly after becoming activated by pathologic signals. CFs contribute to multiple phases of post-MI heart repair and remodeling, including the initial response to CM death, immune cell (IC) recruitment, and fibrotic scar formation. The goal of this review is to describe how resident fibroblasts contribute to the healing and remodeling that occurs after MI, with an emphasis on how fibroblasts communicate with other cell types in the healing infarct scar .
Topics: Animals; Extracellular Matrix; Fibroblasts; Humans; Matrix Metalloproteinases; Myocardial Infarction; Myocardium; Proteoglycans; Transforming Growth Factor beta1; Ventricular Remodeling
PubMed: 33144186
DOI: 10.1016/j.cellsig.2020.109824 -
JACC. Heart Failure Jan 2023
Topics: Humans; Heart Failure; Heart; Myocardium; Biomarkers; Fibrosis; Ventricular Remodeling
PubMed: 36599552
DOI: 10.1016/j.jchf.2022.11.011 -
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 -
Basic Research in Cardiology Nov 2023There remains an unmet need to identify novel therapeutic strategies capable of protecting the myocardium against the detrimental effects of acute ischemia-reperfusion...
There remains an unmet need to identify novel therapeutic strategies capable of protecting the myocardium against the detrimental effects of acute ischemia-reperfusion injury (IRI), to reduce myocardial infarct (MI) size and prevent the onset of heart failure (HF) following acute myocardial infarction (AMI). In this regard, perturbations in mitochondrial morphology with an imbalance in mitochondrial fusion and fission can disrupt mitochondrial metabolism, calcium homeostasis, and reactive oxygen species production, factors which are all known to be critical determinants of cardiomyocyte death following acute myocardial IRI. As such, therapeutic approaches directed at preserving the morphology and functionality of mitochondria may provide an important strategy for cardioprotection. In this article, we provide an overview of the alterations in mitochondrial morphology which occur in response to acute myocardial IRI, and highlight the emerging therapeutic strategies for targeting mitochondrial shape to preserve mitochondrial function which have the future therapeutic potential to improve health outcomes in patients presenting with AMI.
Topics: Humans; Myocardium; Myocardial Infarction; Heart Failure; Myocytes, Cardiac; Mitochondria
PubMed: 37955687
DOI: 10.1007/s00395-023-01019-9 -
Medecine Sciences : M/S May 2022For the last 20 years, integrins have been a therapeutic target of interest in the treatment of fibrotic diseases, particularly regarding the integrins of the αV... (Review)
Review
For the last 20 years, integrins have been a therapeutic target of interest in the treatment of fibrotic diseases, particularly regarding the integrins of the αV family. Initially developed as anti-cancer drugs but with modest benefits, inhibitors of integrins (such as the anti-αV cilengitide) have shown interesting anti-fibrotic effects in different organs including the heart. Cardiac fibrosis is defined as an accumulation of stiff extracellular matrix in the myocardium, and ultimately leads to heart failure, one of the leading causes of mortality worldwide. Understanding the determinants of cardiac fibrosis and the involvement of integrins is a major matter of public health. This review presents the current knowledge on the different types of cardiac fibrosis and their etiologies, and report on first data supporting specific integrin inhibition therapy as a novel anti-fibrotic strategy, in particular to treat cardiac fibrosis.
Topics: Extracellular Matrix; Fibrosis; Humans; Integrins; Myocardium
PubMed: 35608466
DOI: 10.1051/medsci/2022055 -
Nature Metabolism Jan 2023Investigation of multi-omic changes and their effects on regulation of metabolic pathways confirm anaplerotic deficiencies in methylmalonic acidaemia, strengthening the...
Investigation of multi-omic changes and their effects on regulation of metabolic pathways confirm anaplerotic deficiencies in methylmalonic acidaemia, strengthening the need for future therapies aimed at replenishing intermediates of the tricarboxylic acid cycle.
Topics: Myocardium; Citric Acid Cycle
PubMed: 36717753
DOI: 10.1038/s42255-022-00724-4 -
Current Heart Failure Reports Feb 2023Myocardial metabolism is intricately linked to cardiac function. Perturbations of cardiac energy metabolism result in an energy-starved heart and the development of... (Review)
Review
PURPOSE OF REVIEW
Myocardial metabolism is intricately linked to cardiac function. Perturbations of cardiac energy metabolism result in an energy-starved heart and the development of contractile dysfunction. In this review, we discuss alterations in myocardial energy supply, transcriptional changes in response to different energy demands, and mitochondrial function in the development of heart failure.
RECENT FINDINGS
Recent studies on substrate modulation through modifying energy substrate supply have shown cardioprotective properties. In addition, large cardiovascular outcome trials of anti-diabetic agents have demonstrated prognostic benefit, suggesting the importance of myocardial metabolism in cardiac function. Understanding molecular and transcriptional controls of cardiac metabolism promises new research avenues for metabolic treatment targets. Future studies assessing the impact of substrate modulation on cardiac energetic status and function will better inform development of metabolic therapies.
Topics: Humans; Heart Failure; Myocardium; Energy Metabolism; Hypoglycemic Agents; Heart
PubMed: 36800045
DOI: 10.1007/s11897-023-00589-y -
Aging Cell Dec 2023Advancements in longevity research have provided insights into the impact of cardiac aging on the structural and functional aspects of the heart. Notable changes include... (Review)
Review
Advancements in longevity research have provided insights into the impact of cardiac aging on the structural and functional aspects of the heart. Notable changes include the gradual remodeling of the myocardium, the occurrence of left ventricular hypertrophy, and the decline in both systolic and diastolic functions. Macrophages, a type of immune cell, play a pivotal role in innate immunity by serving as vigilant agents against pathogens, facilitating wound healing, and orchestrating the development of targeted acquired immune responses. Distinct subsets of macrophages are present within the cardiac tissue and demonstrate varied functions in response to myocardial injury. The differentiation of cardiac macrophages according to their developmental origin has proven to be a valuable strategy in identifying reparative macrophage populations, which originate from embryonic cells and reside within the tissue, as well as inflammatory macrophages, which are derived from monocytes and recruited to the heart. These subsets of macrophages possess unique characteristics and perform distinct functions. This review aims to summarize the current understanding of the roles and phenotypes of cardiac macrophages in various conditions, including the steady state, aging, and other pathological conditions. Additionally, it will highlight areas that require further investigation to expand our knowledge in this field.
Topics: Heart; Macrophages; Myocardium; Monocytes
PubMed: 37817547
DOI: 10.1111/acel.14008