Salvianolic acid A alleviates heart failure with preserved ejection fraction via regulating TLR/Myd88/TRAF/NF-κB and p38MAPK/CREB signaling pathways DOI Open Access

Awaguli Dawuti,

Shuchan Sun,

Ranran Wang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115837 - 115837

Published: Nov. 6, 2023

Heart failure with preserved ejection fraction (HFpEF) is a morbid, fatal, and common syndrome for which lack of evidence-based therapies. Salvianolic acid A (SAA), major active ingredient Salvia miltiorrhiza Burge, has shown potential to protect against cardiovascular diseases. This study aims elucidate whether SAA possessed therapeutic activity HFpEF explore the mechanism. mouse model was established infusing combination high-fat diet (HFD) Nω-nitro-L-arginine methyl ester (L-NAME) 14 weeks. After 10 weeks feeding, mice were given (2.5, 5, mg/kg) via oral gavage four Body weight, blood pressure, lipids, glucose tolerance, exercise performance, cardiac systolic/diastolic function, pathophysiological changes, inflammatory factors assessed. Experimental results showed that reduced risk factors, such as body weight gain, intolerance, lipid disorders, increased tolerance in mice. Moreover, not only relieved myocardial hypertrophy fibrosis by reducing interventricular septal wall thickness, left ventricular posterior mass, heart index, cardiomyocyte cross-sectional area collagen content, but also improved diastolic function E/E' ratio. Finally, inhibited TLR2/TLR4-mediated Myd88 activation its downstream molecules TRAF6 IRAK4, decreases release proinflammatory cytokines mediators through NF-κB p38 MAPK pathways. In conclusion, could attenuate inflammation disfunction TLR/Myd88/TRAF/NF-κB p38MAPK/CREB signaling pathways mice, provides evidence drug treatment clinic.

Language: Английский

Heart Failure With Preserved Ejection Fraction DOI Creative Commons
Barry A. Borlaug, Kavita Sharma, Sanjiv J. Shah

et al.

Journal of the American College of Cardiology, Journal Year: 2023, Volume and Issue: 81(18), P. 1810 - 1834

Published: April 19, 2023

Language: Английский

Citations

237
Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets DOI
Barry A. Borlaug, Michael D. Jensen, Dalane W. Kitzman

et al.

Cardiovascular Research, Journal Year: 2022, Volume and Issue: 118(18), P. 3434 - 3450

Published: July 26, 2022

Abstract Obesity and heart failure with preserved ejection fraction (HFpEF) represent two intermingling epidemics driving perhaps the greatest unmet health problem in cardiovascular medicine 21st century. Many patients HFpEF are either overweight or obese, recent data have shown that increased body fat its attendant metabolic sequelae widespread, protean effects systemically on system leading to symptomatic HFpEF. The paucity of effective therapies underscores importance understanding distinct pathophysiological mechanisms obese develop novel therapies. In this review, we summarize current non-cardiovascular features phenotype HFpEF, how adiposity might pathophysiologically contribute phenotype, these processes be targeted therapeutically.

Language: Английский

Citations

200
Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models DOI Creative Commons
Jason D. Roh, Joseph A. Hill, Abhilasha Singh

et al.

Circulation Research, Journal Year: 2022, Volume and Issue: 130(12), P. 1906 - 1925

Published: June 9, 2022

Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest challenges facing cardiovascular medicine today. Despite being most common form heart worldwide, there has been limited success in developing therapeutics for this syndrome. This is largely due to our incomplete understanding biology driving its systemic pathophysiology and heterogeneity clinical phenotypes, which are increasingly recognized as distinct HFpEF phenogroups. Development efficacious fundamentally relies on robust preclinical models that not only faithfully recapitulate key features syndrome but also enable rigorous investigation putative mechanisms disease context clinically relevant phenotypes. In review, we propose a research strategy conceptually grounded model diversification aims better align evolving HFpEF. Although often viewed major obstacle research, challenge notion argue embracing it may be demystifying pathobiology. Here, first provide an overarching guideline through stepwise approach comprehensive cardiac extra-cardiac phenotyping. We then present overview currently available models, focused 3 leading phenogroups, primarily based aging, cardiometabolic stress, chronic hypertension. discuss how well these reflect their phenogroup highlight some more recent mechanistic insights they providing into complex underlying

Language: Английский

Citations

99
Glycolipid Metabolic Disorders, Metainflammation, Oxidative Stress, and Cardiovascular Diseases: Unraveling Pathways DOI Creative Commons

Enzo Pereira de Lima,

Renato Cesar Moretti,

Karina Torres Pomini

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(7), P. 519 - 519

Published: July 12, 2024

Glycolipid metabolic disorders (GLMDs) are various resulting from dysregulation in glycolipid levels, consequently leading to an increased risk of obesity, diabetes, liver dysfunction, neuromuscular complications, and cardiorenal vascular diseases (CRVDs). In patients with GLMDs, excess caloric intake a lack physical activity may contribute oxidative stress (OxS) systemic inflammation. This study aimed review the connection between GLMD, OxS, metainflammation, onset CRVD. GLMD is due causing dysfunction synthesis, breakdown, absorption glucose lipids body, excessive ectopic accumulation these molecules. mainly neuroendocrine dysregulation, insulin resistance, metainflammation. many inflammatory markers defense cells play vital role related tissues organs, such as blood vessels, pancreatic islets, liver, muscle, kidneys, adipocytes, promoting lesions that affect interconnected organs through their signaling pathways. Advanced glycation end products, ATP-binding cassette transporter 1, Glucagon-like peptide-1, Toll-like receptor-4, sphingosine-1-phosphate (S1P) crucial since they glucolipid metabolism. The consequences this system organ damage morbidity mortality.

Language: Английский

Citations

24
Flavonoids: Potential therapeutic agents for cardiovascular disease DOI Creative Commons
Yingxue Liu, Jing Luo, Peng Lin

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(12), P. e32563 - e32563

Published: June 1, 2024

Flavonoids are found in the roots, stems, leaves, and fruits of many plant taxa. They related to growth development, pigment formation, protection against environmental stress. function as antioxidants exert anti-inflammatory effects cardiovascular system by modulating classical inflammatory response pathways, such TLR4-NF-ĸB, PI3K-AKT, Nrf2/HO-1 signalling pathways. There is increasing evidence for therapeutic flavonoids on hypertension, atherosclerosis, other diseases. The potential clinical value diseases has been widely explored. For example, studies have evaluated roles regulation blood pressure via endothelium-dependent non-endothelium-dependent pathways myocardial systolic diastolic functions influencing calcium homeostasis smooth muscle-related protein expression. also hypoglycaemic, hypolipidemic, anti-platelet, autophagy, antibacterial effects. In this paper, role mechanism were reviewed order provide reference application future.

Language: Английский

Citations

18
Inflammation in Metabolic Cardiomyopathy DOI Creative Commons
Florian A. Wenzl, Samuele Ambrosini, S A Mohammed

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2021, Volume and Issue: 8

Published: Oct. 4, 2021

Overlapping pandemics of lifestyle-related diseases pose a substantial threat to cardiovascular health. Apart from coronary artery disease, metabolic disturbances linked obesity, insulin resistance and diabetes directly compromise myocardial structure function through independent shared mechanisms heavily involving inflammatory signals. Accumulating evidence indicates that dysregulation causes systemic inflammation, which in turn aggravates disease. Indeed, elevated levels pro-inflammatory cytokines substrates induce an state different cardiac cells lead subcellular alterations thereby promoting maladaptive remodeling. At the cellular level, inflammation-induced oxidative stress, mitochondrial dysfunction, impaired calcium handling, lipotoxicity contribute cardiomyocyte hypertrophy extracellular matrix accumulation microvascular In cardiometabolic patients, inflammation is maintained by innate immune cell activation mediated pattern recognition receptors such as Toll-like receptor 4 (TLR4) downstream NLRP3 inflammasome NF-κB-dependent pathways. Chronic low-grade progressively alters processes heart, leading cardiomyopathy (MC) phenotype eventually heart failure with preserved ejection fraction (HFpEF). accordance preclinical data, observational studies consistently showed increased markers features patients HFpEF. Future treatment approaches MC may target mediators they are closely intertwined nutrient metabolism. Here, we review current on involved development provide overview cytokine-driven effects stratified type.

Language: Английский

Citations

69
Immunometabolic mechanisms of heart failure with preserved ejection fraction DOI Open Access
Gabriele G. Schiattarella, Pilar Alcaide, Gianluigi Condorelli

et al.

Nature Cardiovascular Research, Journal Year: 2022, Volume and Issue: 1(3), P. 211 - 222

Published: March 14, 2022

Language: Английский

Citations

67
Sex differences in heart mitochondria regulate diastolic dysfunction DOI Creative Commons
Yang Cao, Laurent Vergnes, Yu-Chen Wang

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 4, 2022

Heart failure with preserved ejection fraction (HFpEF) exhibits a sex bias, being more common in women than men, and we hypothesize that mitochondrial differences might underlie this bias. As part of genetic studies heart mice, observe DNA levels function tend to be reduced females as compared males. We also expression genes encoding proteins are higher males human cohorts. test our hypothesis panel genetically diverse inbred strains termed the Hybrid Mouse Diversity Panel (HMDP). Indeed, find gene is highly correlated diastolic function, key trait HFpEF. Consistent this, "two-hit" mouse model HFpEF confirm differs between sexes strongly associated number traits. By integrating data from HMDP cohort, identify Acsl6 determinant function. validate its role using adenoviral over-expression heart. conclude underlie, part, bias

Language: Английский

Citations

65
Chronic low‐grade inflammation in heart failure with preserved ejection fraction DOI Creative Commons
Thássio Mesquita, Yen‐Nien Lin, Ahmed Ibrahim

et al.

Aging Cell, Journal Year: 2021, Volume and Issue: 20(9)

Published: Aug. 12, 2021

Abstract Heart failure (HF) with preserved ejection fraction (HFpEF) is currently the predominant form of HF a dramatic increase in risk age. Low‐grade inflammation, as occurs aging (termed “inflammaging”), common feature HFpEF pathology. Suppression proinflammatory pathways has been associated attenuated disease severity and better outcomes. From this perspective, inflammasome signaling plays central role mediating chronic inflammation cardiovascular progression. However, causal link between inflammasome‐immune axis on age‐dependent progression remains conjectural. In review, we summarize current understanding inflammatory cardiac function decline. We will also evaluate recent advances evidence regarding pathway pathophysiology HFpEF, special attention to signaling.

Language: Английский

Citations

59
Cardiac metabolism in HFpEF: from fuel to signalling DOI Open Access
Federico Capone, Cristian Sotomayor-Flores, David Bode

et al.

Cardiovascular Research, Journal Year: 2022, Volume and Issue: 118(18), P. 3556 - 3575

Published: Dec. 7, 2022

Heart failure (HF) is marked by distinctive changes in myocardial uptake and utilization of energy substrates. Among the different types HF, HF with preserved ejection fraction (HFpEF) a highly prevalent, complex, heterogeneous condition for which metabolic derangements seem to dictate disease progression. Changes intermediate metabolism cardiometabolic HFpEF-among most prevalent forms HFpEF-have large impact both on provision number signalling pathways heart. This dual, vs. signalling, role played particular long-chain fatty acids (LCFAs) short-chain carbon sources [namely, (SCFAs) ketone bodies (KBs)]. LCFAs are key fuels heart, but their excess can be harmful, as case toxic accumulation lipid by-products (i.e. lipotoxicity). SCFAs KBs have been proposed potential major, alternative source HFpEF. At same time, substrate protein post-translational modifications other direct indirect pivotal importance HFpEF pathogenesis. An in-depth molecular understanding biological functions substrates will instrumental development novel therapeutic approaches Here, we summarize current evidence HFpEF, discuss metabolites through, at least part, fate modifications, highlight clinical translational challenges around therapy

Language: Английский

Citations

59