Isolated Mouse Adult Cardiomyocytes Display Minimal Mitochondrial ATP Demand and Maximal Reliance on Glycolysis.

Mitochondrial maladaptation is a hallmark of heart failure, contributing to impaired energy production and contractile dysfunction. Understanding the bioenergetics of cardiomyocytes under healthy and pathological conditions is critical for characterizing mitochondrial maladaptation. While adult cardiomyocytes from rodents are a widely used model, recent studies have reported oligomycin insensitivity in these cells, a phenomenon often overlooked.

Transcriptome wide changes in long noncoding RNAs in diabetic ischemic heart disease.

More than 10% of adults in the United States have type 2 diabetes mellitus (DM) with a 2-4 times higher prevalence of ischemic heart disease than the non-diabetics. Despite extensive research approaches to limit this life-threatening condition have proven unsuccessful, highlighting the need for understanding underlying molecular mechanisms. Long noncoding RNAs (lncRNAs), which regulate gene expression by acting as signals, decoys, guides, or scaffolds have been implicated in diverse cardiovascular conditions.

Corrigendum: 1821-2021: contributions of physicians and researchers of Greek descent in the advancement of clinical and experimental cardiology and cardiac surgery.

[This corrects the article DOI: 10.3389/fcvm.2023.

PPARδ activation improves cardiac mitochondrial homeostasis in desmin deficient mice but does not alleviate systolic dysfunction.

Peroxisome proliferator-activated receptor (PPAR) δ is a major transcriptional regulator of cardiac energy metabolism with pleiotropic properties, including anti-inflammatory, anti-oxidative and cardioprotective action. In this study, we sought to investigate whether pharmacological activation of PPARδ via intraperitoneal administration of the selective ligand GW0742 could ameliorate heart failure and mitochondrial dysfunction that have been previously reported in a characterized genetic model of heart failure, the desmin null mice (Des). Our studies demonstrate that treatment of Des mice with the PPARδ agonist attenuated cardiac inflammation, fibrosis and cardiac remodeling.

1821-2021: Contributions of physicians and researchers of Greek descent in the advancement of clinical and experimental cardiology and cardiac surgery.

While the role of Greeks in the development of early western medicine is well-known and appreciated, the contributions of modern Greek medical practitioners are less known and often overlooked. On the occasion of the 200-year anniversary of the Greek War of Independence, this review article sheds light onto the achievements of modern scientists of Greek descent in the development of cardiology, cardiac surgery, and cardiovascular research, through a short history of the development of these fields and of the related institutions in Greece. In the last decades, the Greek cardiology and Cardiac Surgery communities have been active inside and outside Greece and have a remarkable presence internationally, particularly in the United States.

Cardiovascular aging: from cellular and molecular changes to therapeutic interventions.

Progressive age-induced deterioration in the structure and function of the cardiovascular system involves cardiac hypertrophy, diastolic dysfunction, myocardial fibrosis, arterial stiffness, and endothelial dysfunction. These changes are driven by complex processes that are interconnected, such as oxidative stress, mitochondrial dysfunction, autophagy, inflammation, fibrosis, and telomere dysfunction. In recent years, the advances in research of cardiovascular aging, including the wide use of animal models of cardiovascular aging, elucidated an abundance of cell signaling pathways involved in these processes and brought into sight possible interventions, which span from pharmacological agents, such as metformin, sodium-glucose cotransporter 2-inhibitors, rapamycin, dasatinib and quercetin, to lifestyle changes.

The role of glucose in cardiac physiology and pathophysiology.

Purpose Of Review: Heart failure is one of the major causes of death worldwide and continues to increase despite therapeutics and pharmacology advances. Fatty acids and glucose are used as ATP-producing fuels in heart to meet its energy demands. However, dysregulation of metabolites' use plays a pivotal role in cardiac diseases.

Specificity Proteins (SP) and Krüppel-like Factors (KLF) in Liver Physiology and Pathology.

The liver acts as a central hub that controls several essential physiological processes ranging from metabolism to detoxification of xenobiotics. At the cellular level, these pleiotropic functions are facilitated through transcriptional regulation in hepatocytes. Defects in hepatocyte function and its transcriptional regulatory mechanisms have a detrimental influence on liver function leading to the development of hepatic diseases.

Krüppel-like factor (KLF)5: An emerging foe of cardiovascular health.

Krüppel-like factors (KLFs) are DNA-binding transcriptional factors, which regulate various pathways that pertain to development, metabolism and other cellular mechanisms. KLF5 was first cloned in 1993 and by 1999, it was reported as the intestinal-enriched KLF. Beyond findings that have associated KLF5 with normal development and cancer, it has been associated with various types of cardiovascular (CV) complications and regulation of metabolic pathways in the liver, heart, adipose tissue and skeletal muscle.

Metabolic Complications in Cardiac Aging.

Aging is a process that can be accompanied by molecular and cellular alterations that compromise cardiac function. Although other metabolic disorders with increased prevalence in aged populations, such as diabetes mellitus, dyslipidemia, and hypertension, are associated with cardiovascular complications; aging-related cardiomyopathy has some unique features. Healthy hearts oxidize fatty acids, glucose, lactate, ketone bodies, and amino acids for producing energy.

KLF5 Is Induced by FOXO1 and Causes Oxidative Stress and Diabetic Cardiomyopathy.

Rationale: Diabetic cardiomyopathy (DbCM) is a major complication in type-1 diabetes, accompanied by altered cardiac energetics, impaired mitochondrial function, and oxidative stress. Previous studies indicate that type-1 diabetes is associated with increased cardiac expression of KLF5 (Krüppel-like factor-5) and PPARα (peroxisome proliferator-activated receptor) that regulate cardiac lipid metabolism.

Objective: In this study, we investigated the involvement of KLF5 in DbCM and its transcriptional regulation.

Cardiomyocyte Krüppel-Like Factor 5 Promotes De Novo Ceramide Biosynthesis and Contributes to Eccentric Remodeling in Ischemic Cardiomyopathy.

Background: We previously showed that cardiomyocyte Krϋppel-like factor (KLF) 5 regulates cardiac fatty acid oxidation. As heart failure has been associated with altered fatty acid oxidation, we investigated the role of cardiomyocyte KLF5 in lipid metabolism and pathophysiology of ischemic heart failure.

Methods: Using real-time polymerase chain reaction and Western blot, we investigated the KLF5 expression changes in a myocardial infarction (MI) mouse model and heart tissue from patients with ischemic heart failure.

The Glitazars Paradox: Cardiotoxicity of the Metabolically Beneficial Dual PPARα and PPARγ Activation.

The most common complications in patients with type-2 diabetes are hyperglycemia and hyperlipidemia that can lead to cardiovascular disease. Alleviation of these complications constitutes the major therapeutic approach for the treatment of diabetes mellitus. Agonists of peroxisome proliferator-activated receptor (PPAR) alpha and PPARγ are used for the treatment of hyperlipidemia and hyperglycemia, respectively.

Genomic Binding Patterns of Forkhead Box Protein O1 Reveal Its Unique Role in Cardiac Hypertrophy.

Background: Cardiac hypertrophic growth is mediated by robust changes in gene expression and changes that underlie the increase in cardiomyocyte size. The former is regulated by RNA polymerase II (pol II) de novo recruitment or loss; the latter involves incremental increases in the transcriptional elongation activity of pol II that is preassembled at the transcription start site. The differential regulation of these distinct processes by transcription factors remains unknown.

B-type natriuretic peptide is upregulated by c-Jun N-terminal kinase and contributes to septic hypotension.

B-type natriuretic peptide (BNP) is secreted by ventricular cardiomyocytes in response to various types of cardiac stress and has been used as a heart failure marker. In septic patients, increased BNP suggests poor prognosis; however, no causal link has been established. Among various effects, BNP decreases systemic vascular resistance and increases natriuresis that leads to lower blood pressure.

Loss of dynamic regulation of G protein-coupled receptor kinase 2 by nitric oxide leads to cardiovascular dysfunction with aging.

Nitric oxide (NO) and -nitrosothiol (SNO) are considered cardio- and vasoprotective substances. We now understand that one mechanism in which NO/SNOs provide cardiovascular protection is through their direct inhibition of cardiac G protein-coupled receptor (GPCR) kinase 2 (GRK2) activity via -nitrosylation of GRK2 at cysteine 340 (C340). This maintains GPCR homeostasis, including β-adrenergic receptors, through curbing receptor GRK2-mediated desensitization.

Dual peroxisome-proliferator-activated-receptor-α/γ activation inhibits SIRT1-PGC1α axis and causes cardiac dysfunction.

Dual peroxisome proliferator-activated receptor (PPAR)α/γ agonists that were developed to target hyperlipidemia and hyperglycemia in type 2 diabetes patients, caused cardiac dysfunction or other adverse effects. We studied the mechanisms that underlie the cardiotoxic effects of a dual PPARα/γ agonist, tesaglitazar, in wild type and diabetic (leptin receptor deficient - db/db) mice. Mice treated with tesaglitazar-containing chow or high fat diet developed cardiac dysfunction despite lower plasma triglycerides and glucose levels.

Myocardial Strain and Cardiac Output are Preferable Measurements for Cardiac Dysfunction and Can Predict Mortality in Septic Mice.

Background Sepsis is the overwhelming host response to infection leading to shock and multiple organ dysfunction. Cardiovascular complications greatly increase sepsis-associated mortality. Although murine models are routinely used for preclinical studies, the benefit of using genetically engineered mice in sepsis is countered by discrepancies between human and mouse sepsis pathophysiology.

Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21.

Cardiac metabolism affects systemic energetic balance. Previously, we showed that Krüppel-like factor (KLF)-5 regulates cardiomyocyte PPARα and fatty acid oxidation-related gene expression in diabetes. We surprisingly found that cardiomyocyte-specific KLF5 knockout mice (αMHC-KLF5) have accelerated diet-induced obesity, associated with increased white adipose tissue (WAT).

Fatty Acid Oxidation Promotes Cardiomyocyte Proliferation Rate but Does Not Change Cardiomyocyte Number in Infant Mice.

Cardiomyocyte proliferation accounts for the increase of cardiac muscle during fetal mammalian heart development. Shortly after birth, cardiomyocyte transits from hyperplasia to hypertrophic growth. Here, we have investigated the role of fatty acid β-oxidation in cardiomyocyte proliferation and hypertrophic growth during early postnatal life in mice.