Metabolic rewiring and inter-organ crosstalk in diabetic HFpEF

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 4, 2025

Heart failure with preserved ejection fraction (HFpEF) represents a significant and growing clinical challenge. Initially, for an extended period, HFpEF was simply considered as subset of heart failure, manifesting haemodynamic disorders such hypertension, myocardial hypertrophy, diastolic dysfunction. However, the rising prevalence obesity diabetes has reshaped phenotype, nearly 45% cases coexisting diabetes. Currently, it is recognized multi-system disorder that involves heart, liver, kidneys, skeletal muscle, adipose tissue, along immune inflammatory signaling pathways. In this review, we summarize landscape metabolic rewiring crosstalk between other organs/systems (e.g., adipose, gut, liver hematopoiesis system) in diabetic first instance. A diverse array metabolites cytokines play pivotal roles intricate process, rewiring, chronic responses, dysregulation, endothelial dysfunction, fibrosis identified central mechanisms at complex interplay. The liver-heart axis links nonalcoholic steatohepatitis through shared lipid accumulation, inflammation, pathways, while gut-heart dysbiosis-driven trimethylamine N-oxide, indole-3-propionic acid short-chain fatty acids) impacting cardiac function inflammation. Adipose-heart highlights epicardial tissue source local inflammation mechanical stress, whereas hematopoietic system contributes via cell activation cytokine release. We contend that, based on viewpoints expounded breaking inter-organ/system vicious cycle linchpin treating HFpEF.

Language: Английский

Decoding the Liver-Heart Axis in Cardiometabolic Diseases

Circulation Research, Journal Year: 2025, Volume and Issue: 136(11), P. 1335 - 1362

Published: May 22, 2025

The liver and heart are closely interconnected organs, their bidirectional interaction plays a central role in cardiometabolic disease. In this review, we summarize current evidence linking dysfunction—particularly metabolic dysfunction–associated steatotic disease, alcohol-associated cirrhosis—with an increased risk of failure other cardiovascular diseases. We discuss how these conditions contribute to cardiac remodeling, systemic inflammation, hemodynamic stress dysfunction turn impairs perfusion promotes hepatic injury. Particular attention is given the molecular mediators liver-heart communication, including hepatokines cardiokines, as well emerging advanced research methodologies, omics integration, proximity labeling, organ-on-chip platforms, that redefining our understanding interorgan cross talk. By integrating mechanistic insights with translational tools, review aims support development multiorgan therapeutic strategies for

Language: Английский

Sodium–Glucose Cotransporter 2 Inhibitor Ameliorate Angiotensin II-Induced Hypertension and Vascular Injury by Upregulating FGF21

Inflammation, Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

Clinical trials have demonstrated Sodium-glucose cotransporter 2 inhibitors (SGLT2i) antihypertensive effects, yet their underlying mechanisms remain to be fully elucidated. Fibroblast growth factor 21 (FGF21) circulating levels are associated with hypertension in humans. This study aims investigate the roles of SGLT2i and FGF21 improving potential mechanisms. A mouse model Ang II-induced was established. Wild-type (WT) C57BL/6 mice knockout (FGF21-/-) were sequentially treated Angiotensin II (Ang II) dapagliflozin. Blood pressure monitored. Cardiac structure assessed using echocardiography. Serum measured, expression fibroblast receptor 1 (FGFR1) thoracic aorta quantified. Vascular pathology oxidative stress responses evaluated. Human aortic smooth muscle cells (HASMCs) or SGLT2i, knocked down HASMCs explore its mechanism action. increased FGFR. improved systolic blood elevation, myocardial hypertrophy, vascular wall thickening, fibrosis, WT mice. These protective effects reduced FGF21-/- Knockdown abolished SGLT2i-induced upregulation antioxidant markers downregulation TGF-β fibrosis-related proteins. SGLT2i-mediated pressure-lowering primarily achieved through activation FGF21/FGFR1.

Language: Английский