The Role of GLP-1R and GIPR Agonism in Heart Failure DOI
Phelopater Sedrak, Kim A. Connelly

Canadian Diabetes & Endocrinology Today, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Heart failure (HF) is a clinical syndrome characterized by signs and symptoms of structural functional cardiac abnormalities. It corroborated elevated N-terminal pro‑B‑type natriuretic peptide (NT-proBNP) levels objective evidence pulmonary or systemic congestion. More than 100,000 Canadians are diagnosed with HF annually. For years, has been classified based on left ventricular ejection fraction (LVEF). reduced (HFrEF) refers to symptomatic an LVEF <40%. However, if the >50%, this known as preserved (HFpEF). In HFpEF, obesity commonly implicated in disease pathophysiology, present up 80% people condition. Obesity contributes concentric heart remodelling through mechanisms such insulin resistance, diabetes, hyperlipidemia, visceral adipose tissue expansion, myocardial steatosis. Additionally, leads pro-inflammatory state which affects vasculature organs.2 Glucagon‑like peptide-1 receptor agonists (GLP‑1RAs), semaglutide, have shown promise weight reduction across multiple Phase 3 trials. Agents combining GLP-1RA glucose-dependent insulinotropic (GIPR) agonism, tirzepatide, also contributed clinically significant loss. As such, their impact addressing obesity‑related HFpEF under investigation. This paper reviews data GLP-1RAs tirzepatide patients spectrum, particular focus those HFpEF.

Language: Английский

Therapeutic Potential of GLP-1 Receptor Agonists in Diabetes and Cardiovascular Disease: Mechanisms and Clinical Implications DOI Creative Commons

Xinyu Zhang,

Chao Cao, Fei Zheng

et al.

Cardiovascular Drugs and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Glucagon-like peptide-1 (GLP-1) is a crucial incretin hormone secreted by intestinal endocrine L cells. Given its pivotal physiological role, researchers have developed GLP-1 receptor agonists (GLP-1 RAs) through structural modifications. These analogues display pharmacological effects similar to those of but with augmented stability and are regarded as an effective means regulating blood glucose levels in clinical practice. This review aims comprehensively summarize the role RAs management diabetes mellitus (DM) cardiovascular disease (CVD), particular emphasis on underlying signal transduction pathways their therapeutic potential. A comprehensive was carried out literature research. In pancreatic β-cells, regulate secretion insulin glucagon glucosedependent manner influencing signaling such cAMP, PI3K, MAPK. They also contribute regulation promoting proliferation β-cells inhibiting apoptosis these Recent studies demonstrated favorable impact wellbeing. addition protection afforded metabolism regulation, large body evidence from animal cellular has corroborated beneficial conditions heart failure (HF), hypertension, ischemic cardiomyopathy. benefits mainly attributed alleviation inflammatory responses, reduction oxidative stress, prevention cell apoptosis. Clinical data shows that can reduce risk major adverse events (MACE) diabetic patients. play important both diseases. show potential value modulation multiple pathways. However, there may still be some issues practical applications require further research resolution.

Language: Английский

Citations

1
Atrial Fibrosis in Atrial Fibrillation: Mechanistic Insights, Diagnostic Challenges, and Emerging Therapeutic Targets DOI Open Access
Paschalis Karakasis, Panagiotis Theofilis, Panayotis K. Vlachakis

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 209 - 209

Published: Dec. 30, 2024

Atrial fibrosis is a hallmark of atrial cardiomyopathy and plays pivotal role in the pathogenesis fibrillation (AF), contributing to its onset progression. The mechanisms underlying are multifaceted, involving stretch-induced fibroblast activation, oxidative stress, inflammation, coagulation pathways. Variations types-reactive replacement fibrosis-are influenced by patient-specific factors such as age, sex, comorbidities, complicating therapeutic approaches. heterogeneity leads distinct electrophysiological abnormalities that promote AF via reentrant activity enhanced automaticity mechanisms. Despite advancements imaging, late gadolinium enhancement CMR electroanatomical mapping, challenges accurately quantifying persist. Emerging strategies include antifibrotic agents targeting renin-angiotensin-aldosterone system, novel pathways like TGF-β signaling, cardio-metabolic drugs SGLT2 inhibitors GLP-1 receptor agonists. Innovative interventions, including microRNA modulation lipid nanoparticle-based therapies, show promise but require validation. Knowledge gaps remain correlating clinical outcomes with patterns optimizing diagnostic tools. Future research should focus on precise phenotyping, integrating advanced imaging molecular biomarkers, conducting robust trials evaluate therapies' efficacy reducing burden related complications.

Language: Английский

Citations

8
Roles of perivascular adipose tissue in the pathogenesis of atherosclerosis ― an update on recent findings DOI Creative Commons
Tomoya Hara, Masataka Sata

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

Lifestyle-related diseases, such as atherosclerosis and diabetes, are now considered to be a series of diseases caused by chronic inflammation. Adipose tissue is an endocrine organ that not only plays role in lipid storage, heat production, buffering, but also produces physiologically active substances involved Perivascular adipose (PVAT) surrounding blood vessels similarly inflammatory anti-inflammatory act on either directly or via the bloodstream. Epicardial (EAT), which direct contact with coronary arteries inside pericardium, thought have effect well. The presence status these tissues can evaluated imaging tests, has been shown associated current cardiovascular disease (CVD) prognostic factor. It expected become new diagnostic therapeutic target for CVD.

Language: Английский

Citations

0
Weekly Journal Scan: Have we reached the SUMMIT of incretin treatment of heart failure with preserved ejection fraction and obesity? DOI
Giovanna Liuzzo, Carlo Patrono

European Heart Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Language: Английский

Citations

0
Heart Failure DOI
Harlan M. Krumholz

Journal of the American College of Cardiology, Journal Year: 2025, Volume and Issue: 85(7), P. 683 - 684

Published: Feb. 1, 2025

Language: Английский

Citations

0
Epicardial adipose tissue as target of the incretin-based therapies in cardio-metabolic pathologies: a narrative review DOI
Alexandra Pop, Maria D. Dănilă,

Silvia Giuchici

et al.

Canadian Journal of Physiology and Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

The epicardial adipose tissue (EAT) serves in physiological conditions as a mechanical and thermal myocardial protective layer, well readily available lipid-storage unit. In pathological conditions, EAT expansion becomes deleterious is currently recognized an independent risk factor for the progression of cardiovascular diseases. phenotypic shift from to pro-inflammatory/pro-oxidant facilitated by presence metabolic diseases (obesity, syndrome, diabetes), which further increase its dysregulation, favor occurrence complications (mainly atrial fibrillation), promote towards heart failure. Glucagon-like peptide-1 (GLP-1) receptor agonists are novel antidiabetic medications belonging incretin class that have demonstrated efficacy beyond glycemic control, terms weight reduction cardiorenal protection patients with type 2 diabetes mellitus. GLP-1 receptors glucose-dependent insulinotropic polypeptide (GIP) expressed human targeted increasing number pharmacological agonists, pleiotropic effects on structure function. Herein we review literature characterizing benefits GIP activation single dual particular emphasis their highlight role incretin-based therapy management cardiometabolic pathologies.

Language: Английский

Citations

0
Obesity update: cardiovascular risk and therapeutic innovations (focus on semaglutide and tirzepatide) DOI Creative Commons
Luca Di Odoardo, Ottavio Zucchetti, Edoardo Sciatti

et al.

European Heart Journal Supplements, Journal Year: 2025, Volume and Issue: 27(Supplement_3), P. iii137 - iii142

Published: March 1, 2025

Abstract Excess or dysfunctional adipose tissue is a key pathophysiological factor in cardiovascular–kidney–metabolic syndrome. However, until very recently, there was no evidence that pharmacological treatments for obesity could significantly impact major cardiovascular outcomes. Recently, the SELECT study represented first, and to date only, outcome trial conducted context of treatment obesity, subcutaneous (s.c.) semaglutide 2.4 mg first molecule capable leading statistically significant reduction primary composite death, non-fatal myocardial infarction, stroke obese, non-diabetic patients with pre-existing disease. Furthermore, heart failure preserved ejection fraction obesity-related phenotype, s.c. tirzepatide have been shown improve prognosis, functional capacity, quality life. The main limiting factors implementation are by suboptimal adherence due gastrointestinal intolerance, as well reduced accessibility economic sustainability. It therefore necessary wait see how drug regulatory agencies international guidelines will implement specific setting risk obese patients.

Language: Английский

Citations

0
Tirzepatide for Heart Failure and Obesity DOI
Joseph E. Marine, John Mandrola,

Vinay Prasad

et al.

New England Journal of Medicine, Journal Year: 2025, Volume and Issue: 392(16), P. 1659 - 1662

Published: April 23, 2025

Language: Английский

Citations

0
Anti-consumption agents: Tirzepatide and semaglutide for treating obesity-related diseases and addictions, and improving life expectancy DOI Creative Commons
James H. O’Keefe,

William Grant Franco,

Evan L. O’Keefe

et al.

Progress in Cardiovascular Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

3
Clonal Hematopoiesis of Indeterminate Potential and Atrial Fibrillation: Insights into Pathophysiology and Clinical Implications DOI Open Access
Paschalis Karakasis, Panagiotis Theofilis, Eleftheria Lefkou

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2739 - 2739

Published: March 18, 2025

Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a novel risk factor for cardiovascular diseases. CHIP is characterized by the expansion hematopoietic stem cell clones harboring somatic mutations in genes such TET2, DNMT3A, and ASXL1, which are implicated inflammation, atrial remodeling, hypercoagulability. These foster pro-inflammatory pro-thrombotic environment conducive to arrhythmogenesis, thereby linking development progression fibrillation (AF). Mechanistic insights indicate that contributes fibrosis, disrupts calcium signaling, exacerbates oxidative stress, all heighten susceptibility AF. Clinical studies, including epidemiological Mendelian randomization analyses, further support association between an increased both incident progressive AF, with specific TET2 ASXL1 identified significant contributors. Additionally, been linked adverse outcomes elevated rates heart failure, thromboembolism, mortality. Understanding CHIP’s role AF pathophysiology offers opportunities precision medicine approaches, providing avenues early intervention targeted treatment. This review synthesizes current mechanistic clinical evidence on emphasizes its biomarker stratification, explores emerging therapeutic strategies targeting CHIP-associated pathways.

Language: Английский

Citations

0