Konstantinos Drosatos

Konstantinos Drosatos
University of Cincinnati | UC · Pharmacology and Systems Physiology

MSc, PhD
Ohio Eminent Scholar & Professor

About

92
Publications
13,709
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,980
Citations
Introduction
Metabolic Biology, Diabetes, Sepsis, Ischemic Heart Failure, Cardiac Aging
Additional affiliations
December 2021 - present
University of Cincinnati
Position
  • Professor
July 2020 - December 2021
Temple University
Position
  • Professor (Associate)
May 2014 - July 2020
Temple University
Position
  • Professor (Assistant)
Education
October 2020 - April 2021
Temple University
Field of study
  • Leadership Academy '14
September 2002 - May 2007
Boston University
Field of study
  • PhD in Molecular Biology-Biomedicine (research scholar of the University of Crete)
October 2000 - August 2002
University of Crete, Heraklion, Greece
Field of study
  • MSc in Molecular Biology-Biomedicine

Publications

Publications (92)
Article
Healthy hearts rely more on fatty acid (FA) rather than glucose utilization. It remains unclear whether diabetic cardiomyopathy (DbCM) is accounted for by glucotoxicity or lipotoxicity. Previously, we discovered that either insulin deficiency or insulin resistance causes FOXO1-KLF5 activation in human and murine hearts, which drives cardiac lipotox...
Article
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 be...
Article
Full-text available
Research policy and planning for a given country may benefit from reliable data on both its scientific workforce as well as the diaspora of scientists for countries with substantial brain drain. Here we use a systematic approach using Scopus to generate a comprehensive country-level database of all scientists in Greece. Moreover, we expand that dat...
Article
Full-text available
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...
Preprint
Full-text available
Research policy and planning for a given country may benefit from reliable data on both its scientific workforce as well as the diaspora of scientists for countries with substantial brain drain. Here we use a systematic approach using Scopus to generate a comprehensive country-level database of all scientists in Greece. Moreover, we expand that dat...
Article
Background: We previously showed that cardiomyocyte Krüppel-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 rtPCR and Western Blot, we i...
Article
Full-text available
Rationale: Diabetic cardiomyopathy (DbCM) is a major complication in type-1 diabetes (T1D), accompanied by altered cardiac energetics, impaired mitochondrial function and oxidative stress. Previous studies indicate that T1D is associated with increased cardiac expression of Krüppel-like factor-5 (KLF5) and Peroxisome Proliferator Activated Receptor...
Article
Introduction: Our lab previously showed that cardiomyocyte Krüppel-like factor (KLF)-5 regulates cardiac fatty acid oxidation. Various studies have associated heart failure with altered cardiac fatty acid oxidation and lipotoxicity. Hypothesis: Aberrant regulation of KLF5 contributes to pathophysiology and metabolic perturbations in ischemic heart...
Article
Introduction: Cardiomyopathy in type 1 diabetes (T1D) is accompanied by impaired mitochondrial function, oxidative stress and lipotoxicity. We showed that cardiomyocyte (CM) Krüppel-like factor 5 (KLF5) is increased in streptozotocin-induced T1D and induces Peroxisome Proliferator Activated Receptor (PPAR)α in mice. Hypothesis: KLF5 upregulation by...
Article
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...
Article
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...
Article
Full-text available
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 increase...
Article
Nitric oxide (NO) and S-nitrosothiol (SNO) are considered cardio- and vaso-protective 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 S-nitrosylation of GRK2 at cysteine 340 (C340). This ma...
Article
Sepsis-induced cardiomyopathy (SIC) is associated with increased patient mortality. At present, there are no specific therapies for SIC. Previous studies have reported increased ROS and mitochondrial dysfunction during SIC. However, a unifying mechanism remains to be defined. We hypothesized that PKCdelta is required for abnormal calcium handling a...
Article
Full-text available
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...
Article
Objective: Sepsis-induced cardiomyopathy (SIC) is a frequent complication of sepsis that is associated with increased mortality. There are no effective therapies. Oxidative stress and mitochondrial dysfunction are part of the pathophysiology of SIC but the upstream molecular pathways involved are unclear. Methods: We used PKCdelta knock-out (KO) mi...
Article
Cardiomyopathy in type 1 diabetes (T1D) is accompanied by altered cardiac energetics, impaired mitochondrial function and oxidative stress. We showed previously increased cardiac expression of Krüppel-like factor 5 (KLF5) and Peroxisome Proliferator Activated Receptor (PPAR)α at late T1D stage in mice. We confirmed that KLF5 expression is higher in...
Article
Full-text available
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 betwe...
Article
A vast body of literature has established GRK2 as a key player in the development and progression of heart failure. Inhibition of GRK2 improves cardiac function post injury in numerous animal models. In recent years, discovery of several non-canonical GRK2 targets has expanded our view of this kinase. Here, we describe the novel and exciting findin...
Article
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 increas...
Article
Full-text available
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 mic...
Article
Sepsis is the overwhelming systemic immune response to infection, which can result in multiple organ dysfunction and septic shock. Myocardial dysfunction during sepsis is associated with advanced disease and significantly increased in-hospital mortality. Our group has shown that energetic failure and excess reactive oxygen species (ROS) generation...
Article
Increased abundance of GRK2 [G protein–coupled receptor (GPCR) kinase 2] is associated with poor cardiac function in heart failure patients. In animal models, GRK2 contributes to the pathogenesis of heart failure after ischemia-reperfusion (IR) injury. In addition to its role in down-regulating activated GPCRs, GRK2 also localizes to mitochondria b...
Article
Full-text available
Movement of circulating fatty acids (FAs) to parenchymal cells requires their transfer across the endothelial cell (EC) barrier. The multi-ligand receptor cluster of differentiation 36 (CD36) facilitates tissue FA uptake and is expressed in ECs and parenchymal cells such as myocytes and adipocytes. Whether tissue uptake of FAs is dependent on EC or...
Article
Full-text available
Purpose of review: We present a current perspective of epigenetic alterations that can lead to cardiovascular disease (CVD) and the potential of dietary factors to counteract their actions. In addition, we discuss the challenges and opportunities of dietary treatments as epigenetic modifiers for disease prevention and therapy. Recent findings: R...
Article
Full-text available
Under inflammatory conditions, inflammatory cells release reactive oxygen species (ROS) and reactive nitrogen species (RNS) which cause DNA damage. If not appropriately repaired, DNA damage leads to gene mutations and genomic instability. DNA damage checkpoint factors (DDCF) and DNA damage repair factors (DDRF) play a vital role in maintaining geno...
Article
Full-text available
Insufficient hydrogen sulfide (H2S) has been implicated in Type 2 diabetic mellitus (T2DM) and hyperhomocysteinemia (HHcy)-related cardiovascular complications. We investigated the role of H2S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA) of db/db mice fed a high methionine (HM) diet. HM diet (8 weeks) induced HH...
Article
Full-text available
Krüppel-like factors (KLFs) are deoxyribonucleic acid–binding transcriptional factors that regulate various pathways that control metabolism and other cellular mechanisms. Various KLF isoforms have been associated with cellular, organ, or systemic metabolism. Altered expression or activation of KLFs has been linked to metabolic abnormalities, such...
Article
Full-text available
Background -Heart failure (HF) leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. Inter...
Article
Full-text available
Cardiomyopathy frequently complicates sepsis and is associated with increased mortality. Increased cardiac oxidative stress and mitochondrial dysfunction have been observed during sepsis, but the mechanisms responsible for these abnormalities have not been determined. We hypothesized that NADPH oxidase 2 (NOX2) activation could be responsible for s...
Article
Full-text available
Abnormal lipid metabolism may contribute to myocardial injury and remodeling. To determine whether accumulation of very long-chain ceramides occurs in human failing myocardium, we analyzed myocardial tissue and serum from patients with severe heart failure (HF) undergoing placement of left ventricular assist devices and controls. Lipidomic analysis...
Article
Full-text available
Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with...
Article
Krüppel-like factors (KLF) have important roles in metabolism. We previously found that KLF5 is a positive transcriptional regulator of peroxisome proliferator-activated receptor α ( Ppara) , a central regulator of cardiac fatty acid oxidation (FAO). Mice with cardiomyocyte-specific Klf5 ablation ( α MHC-Klf5 -/- ) had reduced cardiac Ppara express...
Article
Full-text available
The heart utilizes large amounts of fatty acids as energy providing substrates. The physiological balance of lipid uptake and oxidation prevents accumulation of excess lipids. Several processes that affect cardiac function, including ischemia, obesity, diabetes mellitus, sepsis, and most forms of heart failure lead to altered fatty acid oxidation a...
Article
Full-text available
Rationale: Fatty acid oxidation is transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR)α and under normal conditions accounts for 70% of cardiac ATP content. Reduced Ppara expression during sepsis and heart failure leads to reduced fatty acid oxidation and myocardial energy deficiency. Many of the transcriptional regula...
Article
Background: Serine palmitoyltransferase (SPT) is the rate-limiting enzyme of de novo ceramide formation.However, ceramides can be produced through various pathways. The role of de novo ceramide synthesis via SPT in cardiac ceramide synthesis in ischemic cardiomyopathy has not been conclusively studied. Hypothesis: Ceramide synthesis via SPT may be...
Article
Full-text available
The G protein-coupled receptor kinase-2 (GRK2) is upregulated in the injured heart and contributes to heart failure pathogenesis. GRK2 was recently shown to associate with mitochondria but its functional impact in myocytes due to this localization is unclear. This study was undertaken to determine the effect of elevated GRK2 on mitochondrial respir...
Article
Inhibition of cardiac fatty acid oxidation (FAO) is considered beneficial after ischemia reperfusion (I/R). Krüppel-like factors (KLF) have an important role in metabolism. In a model of cardiac energetic deficiency (LPS-treated mice), in silico promoter analysis and whole genome array analysis indicated cardiac KLF5 as important regulator of Ppara...
Article
Full-text available
Over 5 million people in the United States suffer from the complications of heart failure (HF), which is a rapidly expanding health complication. Disorders that contribute to HF include ischemic cardiac disease, cardiomyopathies, and hypertension. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family. There...
Article
Full-text available
Sepsis is a systemic inflammatory response that follows bacterial infection. Cardiac dysfunction is an important consequence of sepsis that affects mortality and has been attributed to either elevated inflammation or suppression of both fatty acid and glucose oxidation and eventual ATP depletion. Moreover, cardiac adrenergic signaling is compromise...
Article
Krüppel-like factors (KLF) affect metabolism. Lipopolysaccharide-induced sepsis reduced cardiac PPARα and increased KLF5 (8-fold) more than any cardiac KLF isoform detected by whole genome microarray analysis. In silico analysis of ppara gene promoter predicted two KLF5 binding sites that overlap with c-Jun (AP-1) binding sites: -792/-772 bp and -7...
Article
Circulating fatty acids must cross the endothelial cell (EC) barrier to supply cardiomyocytes (CM). How this occurs is unknown. Cluster of differentiation (CD) 36 is a membrane associated protein whose total body deletion leads to reduced uptake of non-esterified fatty acids by heart, skeletal muscle and adipose tissue. To determine the contributio...
Article
Full-text available
Objective: Diabetic hypertriglyceridemia is thought to be primarily driven by increased hepatic de novo lipogenesis. However, experiments in animal models indicated that insulin deficiency should decrease hepatic de novo lipogenesis and reduce plasma triglyceride levels. Approach and results: To address the discrepancy between human data and gen...
Article
Full-text available
Fatty acids (FAs) are the primary source for cardiac energy utilization. They account for 70% of myocardial ATP production and glucose; lactate and ketones account for the remaining 30%.1 Earlier studies have suggested that esterified FAs are the major source of cardiac lipids in humans.2 A significant portion of FAs utilized by the heart are deriv...
Chapter
Full-text available
Lipids are the major substrate for cardiac ATP production and they are derived from adipose tissue or lipoprotein triglycerides. Lipoproteins are synthesized in the liver and they obtain their mature form following interaction with enzymes that are present in the circulation. Lipoprotein-derived fatty acids are released by lipoprotein lipase and ar...
Article
Krüppel-like factors (KLF) have been associated with metabolic phenotypes. Our study focused on the metabolic role of cardiac KLF5, as it showed the highest increase among all KLFs that were detected by whole genome microarrays of energy-starved hearts obtained from lipopolysaccharide (LPS)-treated mice. Analysis of ppara promoter indicated two pot...
Article
Full-text available
Both obesity and diabetes mellitus are associated with alterations in lipid metabolism as well as a change in bone homeostasis and osteoclastogenesis. We hypothesized that increased fatty acid levels affect bone health by altering precursor cell differentiation and osteoclast activation. Here we show that palmitic acid (PA, 16:0) enhances RANKL-sti...
Article
Full-text available
Rationale: Efficient clearance of apoptotic cells (efferocytosis) is a prerequisite for inflammation resolution and tissue repair. After myocardial infarction, phagocytes are recruited to the heart and promote clearance of dying cardiomyocytes. The molecular mechanisms of efferocytosis of cardiomyocytes and in the myocardium are unknown. The injur...
Article
Full-text available
Background: Cardiac dysfunction with sepsis is associated with both inflammation and reduced fatty acid oxidation. We hypothesized that energy deprivation accounts for sepsis-related cardiac dysfunction. Methods and results: Escherichia coli lipopolysaccharide (LPS) administered to C57BL/6 mice (wild type) induced cardiac dysfunction and reduced...
Article
Full-text available
: Fish oil (FO) supplementation may improve cardiac function in some patients with heart failure, especially those with diabetes. To determine why this occurs, we studied the effects of FO in mice with heart failure either due to transgenic expression of the lipid uptake protein acyl CoA synthetase 1 (ACS1) or overexpression of the transcription fa...
Article
Full-text available
Adipose fat storage is thought to require uptake of circulating triglyceride (TG)-derived fatty acids via lipoprotein lipase (LpL). To determine how LpL affects the biology of adipose tissue, we created adipose-specific LpL knock-out (ATLO) mice, and we compared them with whole body LpL knock-out mice rescued with muscle LpL expression (MCK/L0) and...