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Gaetano Santulli

Gaetano Santulli

MD, PhD
Associate Professor of Cardiology

About

404
Publications
77,180
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8,671
Citations
Additional affiliations
April 2011 - present
New York Presbyterian Hospital
Position
  • Columbia University Medical Center
January 2004 - present
University of Naples Federico II
Position
  • UNINA

Publications

Publications (404)
Article
The type 2 ryanodine receptor (RyR2) is a Ca2+ release channel on the endoplasmic reticulum (ER) of several types of cells, including cardiomyocytes and pancreatic β cells. In cardiomyocytes, RyR2-dependent Ca2+ release is critical for excitation-contraction coupling; however, a functional role for RyR2 in β cell insulin secretion and diabetes mell...
Article
Calcium (Ca2+) released from the sarcoplasmic reticulum (SR) is crucial for excitation–contraction (E–C) coupling. Mitochondria, the major source of energy, in the form of ATP, required for cardiac contractility, are closely interconnected with the SR, and Ca2+ is essential for optimal function of these organelles. However, Ca2+ accumulation can im...
Article
Tirzepatide has relatively rapid and strong antihypertensive effects (as evidenced by a decrease from baseline in systolic blood pressure of 6.5 mm Hg in the group that received the 15-mg dose). The antihypertensive effect of tirzepatide should not depend on the regulation of the insulin level; indeed, since insulin has been shown to stimulate bot...
Article
Objective: To assess whether the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improves cognitive impairment in frail older adults with diabetes and heart failure with preserved ejection fraction (HFpEF). Research design and methods: We designed a prospective study to assess cognitive and physical function in consecutive frail o...
Article
Background: Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, and both these conditions are associated with endothelial dysfunction and oxidative stress. We investigated the functional role of the SGLT2 (sodium glucose cotransporter 2) inhibitor empagliflozin in frail diabetic and hypertensive o...
Article
Full-text available
T-cell immunoglobulin and mucin domain 1 (TIM-1) has been recently identified as one of the factors involved in the internalization of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human cells, in addition to angiotensin-converting enzyme 2 (ACE2), trans-membrane serine protease 2 (TMPRSS2), neuropilin-1, and others. We hypoth...
Article
Growing evidence correlate the accrual of the sphingolipid ceramide in plasma and cardiac tissue with heart failure (HF). Regulation of sphingolipid metabolism in the heart and the pathological impact of its derangement remain poorly understood. Recently, we discovered that Nogo-B, a membrane protein of endoplasmic reticulum, abundant in the vascul...
Article
Background: Frailty is a multidimensional condition very common in older adults that leads to physical impairment. Frail older adults have an increased risk of adverse outcomes such as disability, hospitalization, and mortality. Hypertension and diabetes are prevailing comorbidities in frail elders. Methods: We studied consecutive frail older patie...
Article
Full-text available
Background Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type 2 diabetes mellitus (T2DM). They have also gained interest for their potential anti-arrhythmic role and their ability to reduce the occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs)...
Article
BACKGROUND: Emerging evidence suggests that elevated levels of high-density lipoprotein cholesterol (HDL-C) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular (CV) events has never been investigated in hypertensive patients. METHODS: In order to fill th...
Article
Introduction: Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms. Method...
Article
-Aims: Growing evidence correlates the accrual of the sphingolipid ceramide in plasma and cardiac tissue with heart failure (HF). Regulation of sphingolipid metabolism in the heart and the pathological impact of its derangement remain poorly understood. Recently, we discovered that Nogo-B, a membrane protein of endoplasmic reticulum, abundant in th...
Article
Methylenetetrahydrofolate reductase (MTHFR) is anenzyme involved in the metabolism of folic acid (VitaminB9), being responsible for the catalysis of 5,10-methyltet-rahydrofolate to 5-methyltetrahydrofolate (an irreversible reduction that is NADPH-dependent) to obtain methionine from re-methylation of homocysteine. Dozens of DNA sequence variants ha...
Article
Full-text available
Emerging evidence has shown that microRNAs (miRNAs) play critical role in the pathogenesis of several disorders. In the present minireview, we focus our attention on the functional role of a specific miRNA, namely miR-34a, in the pathophysiology of frailty and diabetes mellitus. Based on the current literature, we speculate that this miRNA may serv...
Article
Endothelial dysfunction represents a key mechanism underlying heart failure with preserved ejection fraction (HFpEF), diabetes mellitus (DM), and frailty. However, reliable biomarkers to monitor endothelial dysfunction in these patients are lacking. In this study, we evaluated the expression of a panel of circulating microRNAs (miRs) involved in th...
Article
Fabry disease (FD) is a lysosomal storage disorder caused by mutations in the gene for alpha-galactosidase A (GAL) inducing a progressive accumulation of globotriaosylceramide (Gb3) and its metabolites in different organs and tissues. GB3 deposition does not fully explain the clinical manifestations of FD, and other pathogenetic mechanisms have bee...
Article
Full-text available
Background: The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hyp...
Article
We hypothesized that exosomal microRNAs (miRNAs) could be implied in the pathogenesis of thromboembolic complications in COVID-19. We isolated circulating exosomes from COVID-19 patients and then we divided our population in two arms based on the D-dimer level on hospital admission. We observed that exosomal miR-145 and miR-885 significantly correl...
Article
Full-text available
The global prevalence of obesity nearly tripled between 1975 and 2016, making it one of the current biggest challenges for health care. In the United States, obesity affects about 40% of the adult population, and a substantial increase in obesity prevalence has been detected in low-income and middle-income nations. High values of body mass index ar...
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Full-text available
We are delighted to share with you our eleventh Journal Club and highlight some of the most interesting papers published recently. We hope to keep you up-to-date with noncoding RNA research that is outside your study area. The Non-Coding RNA Scientific Board wishes you an exciting and fruitful read.
Article
Full-text available
The new 2022 Guidelines on the management of heart failure (HF) have been recently published replacing those from 2013 and 2017. These guidelines reflect a collaboration between the American Heart Association (AHA), the American College of Cardiology (ACC), and the Heart Failure Society of America (HFSA), incorporating many recent studies, providin...
Article
Full-text available
Cognitive impairment is a prevailing event in hypertensive patients and in frail older adults. Endothelial dysfunction has been shown to underlie both hypertension and cognitive dysfunction. Our hypothesis is that L-Arginine, which is known to ameliorate endothelial dysfunction, could counteract cognitive impairment in a high-risk population of hyp...
Article
Full-text available
Human induced pluripotent stem cells (hiPSCs) can be used to generate various cell types of human body; hiPSC-derived CMs (hiPSC-CMs) represent significant cell source for disease modeling, drug testing and regenerative medicine. Immaturity of hiPSC-CMs in 2D culture limit their applications. Cardiac tissue engineering provides a new promise for bo...
Article
Omega 3 polyunsaturated fatty acids (n-3 PUFA) are known to have beneficial effects on cardiovascular and metabolic health. However, whether different sources of n-3 PUFA, for instance fatty fish vs vegetable oils, could elicit different effects on glucose and lipid metabolism, remains to be determined. Herein we examine recent findings showing tha...
Article
Cardiac rehabilitation (CR) following acute myocardial infarction (AMI) improves physical capacities and decreases hospitalizations and cardiovascular mortality. L-Arginine is the substrate used by nitric oxide (NO) synthase (NOS) to generate NO and it has been shown to exert its beneficial effects on endothelium driving vasodilatation, reducing in...
Article
Full-text available
Background: The qualification and order of authorship in scientific manuscripts are the main disputes in collaborative research work. Objective: The aim of this project was to develop an open-access web-based platform for objective decision-making of authorship qualification and order in medical and science journals. Methods: The design science p...
Article
Background: Hypertension is common in older adults and its incidence increases with age. We investigated the correlation between physical and cognitive impairment in older adults with frailty and hypertension during the COVID-19 pandemic. Methods: We recruited frail hypertensive older adults between March 2021 and December 2021. Global cognitive fu...
Article
Full-text available
microRNAs (miRNA, miRs) play crucial roles in cardiovascular disease regulating numerous processes, including inflammation, cell proliferation, angiogenesis, and cell death. Herein, we present an updated and comprehensive overview of the functional involvement of miRs in the regulation of cardiomyocyte death, a central event in acute myocardial inf...
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Full-text available
After an ischemic injury, the heart undergoes a complex process of structural and functional remodeling that involves several steps, including inflammatory and fibrotic responses. In this review, we are focusing on the contribution of microRNAs in the regulation of inflammation and fibrosis after myocardial infarction. We summarize the most updated...
Article
OBJECTIVE To assess whether the sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improves cognitive impairment in frail older adults with diabetes and heart failure with preserved ejection fraction (HFpEF). RESEARCH DESIGN AND METHODS We designed a prospective study to assess cognitive and physical function in consecutive frail older...
Article
BACKGROUND: Frailty is a multidimensional condition typical of elders that determines physical decline. Frail older adults have a high-risk of functional decline, hospitalization, and mortality. Hyperglycemia (HG) is frequently observed in frail older adults, and it represents an independent predictor of worst outcomes, with or without diabetes mel...
Article
Full-text available
Restenosis, defined as the re-narrowing of an arterial lumen after revascularization, represents an increasingly important issue in clinical practice. Indeed, as the number of stent placements has risen to an estimate that exceeds 3 million annually worldwide, revascularization procedures have become much more common. Several investigators have dem...
Article
Sortilin is a glycoprotein mainly known for its role as a trafficking molecule directing proteins to specific secretory or endocytic compartments of the cell. Its actual contribution to essential hypertension has remained hitherto elusive. Combining top-notch in vivo, ex vivo, and in vitro approaches to clinical investigations, Di Pietro et al. exp...
Article
P-Wave Dispersion (PWD) is an ECG parameter defined as the difference between the longest and the shortest P-Wave duration. PWD has been associated with hypertension, a leading cause of age-related cognitive decline. Moreover, hypertension is associated with vascular dementia and Alzheimer’s Disease. Based on these considerations, we evaluated PWD...
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Full-text available
BACKGROUND: Diabetes and hypertension are common in older adults and represent established risk factors for frailty, a multidimensional condition due to reserve loss and susceptibility to stressors with a high risk of death, hospitalizations, functional and cognitive impairment. Comorbidities such as diabetes and hypertension play a key role in inc...
Article
Full-text available
Background – The association of physical impairment and cognitive decline has never been investigated in frail patients with acute myocardial infarction. Aim - The aim of our study is to assess the correlation between physical and cognitive decline in frail patients with ST-elevation myocardial infarction (STEMI). Methods - We examined consecutive...
Chapter
Full-text available
Emerging evidence has demonstrated that microRNAs (miRNAs or miRs) play functional roles in the regulation of numerous processes in health and disease. Herein we are presenting a systematic review of the functional contribution of miRNAs to the pathophysiology of diabetes mellitus and its complications.
Article
Patients with heart failure (HF) have augmented vascular tone, which increases cardiac workload, impairing ventricular output and promoting further myocardial dysfunction. The molecular mechanisms underlying the maladaptive vascular responses observed in HF are not fully understood. Vascular smooth muscle cells (VSMCs) control vasoconstriction via...
Article
Obstructive sleep apnea (OSA) is defined as brief and repeated interruptions of breathing due to upper airway obstructive events during the sleep; these recurrent interruptions could be complete (apneas) and/or partial (hypopneas), resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. The apnea-hypopnea index (AHI) qu...
Article
Introduction: Neuropilin-1 has been recently identified as a co-factor needed for the entry of SARS-CoV-2 in host cells and has been linked to neurologic symptoms of COVID-19 (Science 2020). Emerging evidence indicates that exosomal microRNAs (miRNAs) are involved in a number of physiologic and pathologic processes. However, to our knowledge, exoso...
Article
Finding reliable parameters to identify patients with heart failure (HF) that will respond to cardiac resynchronization therapy (CRT) represents a major challenge. Post-translational modifications of Ryanodine Receptor (RyR) have been demonstrated in several tissues (including skeletal muscle and circulating lymphocytes) of patients with advanced H...
Article
Introduction: We and others have shown that endothelial cells (ECs) play a pivotal role in COVID-19. In recent years mounting data demonstrated the importance of mitochondria in endothelial dysfunction. Methods: We obtained plasma samples of patients hospitalized with COVID-19 on the first day of hospital admission. Samples were then divided into s...
Article
Introduction: Following an ischemic injury, the persistence of cardiac myofibroblast (myo-FBs) contributes to fibrosis and adverse myocardial remodeling, especially if myoFBs remain active in otherwise healthy areas of the heart, away from the site of injury. The exact mechanisms underlying myo-FB activation and persistence remain unknown. Hypothe...
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Full-text available
Introduction: Minimally invasive extracorporeal circulation (MiECC) reduced inflammatory burden, leading to best clinical outcomes in patients treated with coronary artery bypass grafting (CABG). Despite this, the patients with type 2 diabetes mellitus (T2DM) vs those without T2DM (non-T2DM) have a worse prognosis, caused by over-inflammation and m...
Article
Full-text available
L-Arginine is involved in many different biological processes and recent reports indicate that it could also play a crucial role in the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present an updated over-view of the current evidence on the functional contribution of L-A...
Article
Full-text available
Background Despite primary percutaneous coronary intervention (PPCI) is generally considered the best therapy in older frail adults with ST-segment elevation myocardial infarction (STEMI), the incidence of re-hospitalization for cardiovascular diseases remains significant in these patients. Aims We hypothesized that thrombus aspiration (TA) before...
Article
https://doi.org/10.7326/J21-0016 Source citation: AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial. Eur Heart J. 2021;42:4731-9. 34453840.
Article
Heart failure and cardiovascular disorders represent the leading cause of death in diabetic patients. Here we present a systematic review of the main mechanisms underlying the development of diabetic cardiomyopathy. We also provide an excursus on the relative contribution of cardiomyocytes, fibroblasts, endothelial and smooth muscle cells to the pa...
Article
Background: Primary Percutaneous Coronary Intervention (PPCI) is the best therapeutic choice in frail older adults with ST-Elevation Myocardial Infarction (STEMI). Nevertheless, the incidence of mortality, re-hospitalization and disability remains elevated. Cognitive impairment is one of the most common disability after STEMI in frailty. Objectives...
Article
Full-text available
We are delighted to share with you our ninth Journal Club and highlight some of the most interesting papers published recently [...]
Article
Background: L-Arginine is an amino acid involved in nitric oxide production regulating vascular tone and cardiovascular homeostasis. Hypertension is one of the most common comorbidities worldwide, and leads to endothelial dysfunction contributing to atherosclerosis, inflammation, and oxidative stress. Frailty is a syndrome of decreased physiologica...
Article
We created the new "Cardiovascular Endocrinology" section of "Frontiers in Endocrinology" (Editor-in-Chief: Prof. Gaetano Santulli, MD, PhD) as the perfect home for high-quality research across all aspects of cardiovascular endocrinology
Article
Full-text available
Background. We and others have previously demonstrated that the endothelium is a primary target of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and L-arginine has been shown to improve endothelial dysfunction. However, the effects of L-arginine have never been evaluated in coronavirus disease 2019 (COVID-19). Methods. This is...
Article
Full-text available
Levels of microRNAs (miRNAs) within extracellular vesicles (EVs) have been shown to be useful diagnostic and prognostic biomarkers in a number of disease states. However, EVs miRNAs have never been investigated in COVID-19. We recently demonstrated that miR-24 is expressed in human brain endothelial cells (ECs) and targets Neuropilin-1, a co-factor...
Article
Full-text available
Endothelial dysfunction is a key hallmark of hypertension, which is a leading risk factor for cognitive decline in older adults with or without frailty. Similarly, hyperglycemia is known to impair endothelial function and is a predictor of severe cardiovascular outcomes, independent of the presence of diabetes. On these grounds, we designed a study...
Article
ST-elevation myocardial infarction (STEMI) is one of the leading causes of death and hospitalization worldwide. Hyperglycemia (HG) has been shown to adversely affect STEMI clinical outcomes, leading to higher mortality and severe complications. The aim of our study was to investigate the impact of HG at hospital admission on the risk of restenosis...
Article
We previously demonstrated that the selective retinoic acid receptor (RAR) β2 agonist AC261066 reduces oxidative stress in an ex vivo murine model of ischemia/reperfusion. We hypothesized that by decreasing oxidative stress and consequent fibrogenesis, AC261066 could attenuate the development of contractile dysfunction in post-ischemic heart failur...
Article
Full-text available
Substantial evidence indicates that microRNA-155 (miR-155) plays a crucial role in the pathogenesis of diabetes mellitus (DM) and its complications. A number of clinical studies reported low serum levels of miR-155 in patients with type 2 diabetes (T2D). Preclinical studies revealed that miR-155 partakes in the phenotypic switch of cells within the...
Article
-Background. Beta Hydroxybutyrate (BHB) is the main ketone body produced during fasting or carbohydrate deprivation as an alternative fuel. A key aspect of metabolic remodeling in heart failure (HF) is the down-regulation of fatty acid utilization. Moreover, the myocardial metabolic profile reveals that the failing heart shift towards oxidizing ket...