Heart Failure Reviews, Год журнала: 2024, Номер unknown
Опубликована: Сен. 13, 2024
Язык: Английский
Cardiovascular Research, Год журнала: 2025, Номер unknown
Опубликована: Янв. 31, 2025
Язык: Английский
Процитировано
1
Circulation Research, Год журнала: 2025, Номер 136(1), С. 135 - 157
Опубликована: Янв. 2, 2025
This review examines the giant elastic protein titin and its critical roles in heart function, both health disease, as discovered since identification nearly 50 years ago. Encoded by TTN (titin gene), has emerged a major disease locus for cardiac disorders. Functionally, acts third myofilament type, connecting sarcomeric Z-disks M-bands, regulating myocardial passive stiffness stretch sensing. Its I-band segment, which includes N2B element PEVK (proline, glutamate, valine, lysine-rich regions), serves viscoelastic spring, adjusting sarcomere length force response to stretch. The details how alternative splicing of pre-mRNA produces different isoforms that greatly impact tension under physiological pathological conditions. Key posttranslational modifications, especially phosphorylation, play crucial titin’s stiffness, allowing rapid adaptation changing hemodynamic demands. Abnormal modifications dysregulation are linked diseases such failure with preserved ejection fraction, where increased impairs diastolic function. In addition, discusses importance A-band region setting thick filament enhancing Ca² + sensitivity, contributing Frank-Starling Mechanism heart. truncating variants frequently associated dilated cardiomyopathy, outlines potential mechanisms, including haploinsufficiency, disarray, altered regulation. Variants have also been conditions peripartum cardiomyopathy chemotherapy-induced cardiomyopathy. Therapeutic avenues explored, targeting factors RBM20 (RNA binding motif 20) adjust isoform ratios or using engineered tissues study mechanisms. Advances genetic engineering, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), offer promise modifying treat titin-related cardiomyopathies. comprehensive highlights structural, mechanical, signaling function mutations on diseases.
Язык: Английский
Процитировано
0
Cardiovascular Diabetology, Год журнала: 2025, Номер 24(1)
Опубликована: Фев. 7, 2025
Heart failure with preserved ejection fraction (HFpEF) is a prevalent and complex condition limited effective treatments. Endothelial dysfunction significant component of HFpEF pathophysiology, glucagon-like peptide-1 receptor (GLP-1R) agonists have shown potential benefits in improving endothelial function. This study aims to explore the relationship between mechanisms action GLP-1R agonists, highlighting their therapeutic benefits. A comprehensive review literature was conducted examine etiology HFpEF, role dysfunction, effects on function heart outcomes. The findings indicate that associated various comorbidities, such as obesity, diabetes mellitus, hypertension, which contribute dysfunction. including semaglutide liraglutide, demonstrated cardioprotective effects, vascular function, reducing inflammation, preventing atherosclerosis. Clinical trials, STEP-HFpEF trial, positive results symptoms physical restrictions patients. present promising option for by targeting other pathophysiological mechanisms. Further research needed elucidate precise through exert establish long-term safety efficacy diverse populations.
Язык: Английский
Процитировано
0
Cardiovascular Drugs and Therapy, Год журнала: 2025, Номер unknown
Опубликована: Апрель 2, 2025
Язык: Английский
Процитировано
0
Heart Failure Reviews, Год журнала: 2024, Номер unknown
Опубликована: Сен. 16, 2024
Abstract Heart failure with preserved ejection fraction (HFpEF) is rapidly growing as the most common form of heart failure. Among HFpEF phenotypes, cardiometabolic/obese — driven by cardiometabolic alterations emerges one prevalent forms this syndrome and on which recent therapeutic success have been made. Indeed, pharmacological approaches sodium-glucose cotransporter type 2 inhibitors (SGLT2i) glucagon-like peptide-1 receptor agonists (GLP-1RA) proved to be effective due metabolic protective effects. Similarly, lifestyle changes, including diet exercise are crucial in management. Increasing evidence supports important role physical activity pathogenesis, prognosis, potential reversal HFpEF. Metabolic derangements systemic inflammation key features represent main targets interventions. However, underlying mechanisms beneficial effects these interventions incompletely understood. Hence, there an unmet need tailored intervention modalities for patients Here we present current available management therapeutics, discussing their mechanisms.
Язык: Английский
Процитировано
3
Arhiv za farmaciju, Год журнала: 2024, Номер 74(3), С. 460 - 482
Опубликована: Янв. 1, 2024
Obesity is a chronic, progressive, and recurring disease. The prevalence of obesity has reached pandemic proportions, along with overweight-related conditions like diabetes, cardiovascular diseases, certain cancers. Reducing residual morbidity the main goal treatment. Pharmacotherapy intended for patients who have not responded to lifestyle interventions. There are currently six anti-obesity medications (orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide, tirzepatide) approved long-term management. Most them, except orlistat, predominantly act centrally by increasing satiety, as well reducing appetite food reward. most effective drugs semaglutide tirzepatide, which might provide weight loss more than 10% initial weight. Although all been demonstrated improve cardiometabolic risk factors, only liraglutide lower major events in or without established A personalized approach, considering both drug (weight-reducing capacity safety) patient (comorbidities, age, patient's preferences) features, guarantees best results. In this article, we will critically appraise efficacy safety those pipeline.
Язык: Английский
Процитировано
1
Heart Failure Reviews, Год журнала: 2024, Номер unknown
Опубликована: Сен. 13, 2024
Язык: Английский
Процитировано
1