Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases

Nature Reviews Cardiology, Journal Year: 2021, Volume and Issue: 18(7), P. 499 - 521

Published: Feb. 22, 2021

Language: Английский

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Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(4), P. 1745 - 1807

Published: May 5, 2021

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to rapidly increased overweight obesity. To this point, epidemiological, clinical, experimental evidence supports existence unique disease entity termed "obesity cardiomyopathy," which develops independent hypertension, coronary disease, other diseases. Our contemporary review evaluates for pathological condition, examines putative responsible mechanisms, discusses therapeutic options disorder. Clinical findings have consolidated presence left ventricular dysfunction Experimental investigations uncovered pathophysiological changes myocardial structure function genetically predisposed diet-induced Indeed, consolidates wide array cellular molecular mechanisms underlying etiology obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover free fatty acids, lipotoxicity, amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, fibrosis, dampened flow reserve, microvascular (microangiopathy), endothelial impairment. Given important role risk failure, that with preserved systolic recent rises COVID-19-associated cardiovascular mortality, should provide compelling cardiomyopathy, various comorbid conditions, offer new insights into potential approaches (pharmacological lifestyle modification) clinical management cardiomyopathy.

Language: Английский

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Heart failure in diabetes

Metabolism, Journal Year: 2021, Volume and Issue: 125, P. 154910 - 154910

Published: Oct. 8, 2021

Language: Английский

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Mitochondrial Structure and Function in Human Heart Failure

Circulation Research, Journal Year: 2024, Volume and Issue: 135(2), P. 372 - 396

Published: July 4, 2024

Despite clinical and scientific advancements, heart failure is the major cause of morbidity mortality worldwide. Both mitochondrial dysfunction inflammation contribute to development progression failure. Although crucial reparative healing following acute cardiomyocyte injury, chronic damages heart, impairs function, decreases cardiac output. Mitochondria, which comprise one third volume, may prove a potential therapeutic target for Known primarily energy production, mitochondria are also involved in other processes including calcium homeostasis regulation cellular apoptosis. Mitochondrial function closely related morphology, alters through dynamics, thus ensuring that needs cell met. However, failure, changes substrate use lead impaired myocyte function. This review discusses cristae role contact site organizing system complex ultrastructure changes. Additionally, this covers mitochondria-endoplasmic reticulum sites, communication via nanotunnels, altered metabolite production during We highlight these often-neglected factors promising targets

Language: Английский

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The mitochondrial permeability transition pore: an evolving concept critical for cell life and death

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Journal Year: 2021, Volume and Issue: 96(6), P. 2489 - 2521

Published: June 21, 2021

In this review, we summarize current knowledge of perhaps one the most intriguing phenomena in cell biology: mitochondrial permeability transition pore (mPTP). This phenomenon, which was initially observed as a sudden loss inner membrane impermeability caused by excessive calcium, has been studied for almost 50 years, and still no definitive answer provided regarding its mechanisms. From initial consideration an vitro artifact to notion that mPTP is phenomenon with physiological pathological implications, long road travelled. We here role mitochondria cytosolic calcium control evolving concepts (mPT) mPTP. show how models mechanisms, involve many proposed protein components, have arisen from methodological advances more complex biological models. describe scientific progress allowed milestone discoveries on regulation composition recognition valid target drug development critical component biology.

Language: Английский

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ER Stress in Cardiometabolic Diseases: From Molecular Mechanisms to Therapeutics

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 42(6), P. 839 - 871

Published: March 8, 2021

The endoplasmic reticulum (ER) hosts linear polypeptides and fosters natural folding of proteins through ER-residing chaperones enzymes. Failure the ER to align compose proper protein architecture leads accumulation misfolded/unfolded in lumen, which disturbs homeostasis provoke stress. Presence stress initiates cytoprotective unfolded response (UPR) restore or instigates a rather maladaptive UPR promote cell death. Although wide array cellular processes such as persistent autophagy, dysregulated mitophagy, secretion proinflammatory cytokines may contribute onset progression cardiometabolic diseases, it is well perceived that also evokes development particularly cardiovascular diseases (CVDs), diabetes mellitus, obesity, chronic kidney disease (CKD). Meanwhile, these pathological conditions further aggravate stress, creating vicious cycle. Here this review, we aimed at summarizing updating available information on CVDs, CKD, hoping offer novel insights for management comorbidities regulation

Language: Английский

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Double-activation of mitochondrial permeability transition pore opening via calcium overload and reactive oxygen species for cancer therapy

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: April 12, 2022

Abstract Background Calcium ions (Ca 2+ ) participates in various intracellular signal cascades and especially plays a key role pathways relevant to cancer cells. Mitochondrial metabolism stimulated by calcium overload can trigger the opening of mitochondrial permeability transition pore (MPTP), which leads cell death. Methods Herein, pathway for tumour growth inhibition was built via double-activation MPTP channel. Fe doped covalent organic frameworks (COF) synthesised applied as template grow CaCO 3 shell. Then O 2 storaged into COF, forming -FeCOF@CaCO nanocomposite. After modification with folic acid (FA), @FA (OFCCF) target breast cells realize PDT/Ca synergistic treatment. Results COF induce production 1 under 650 nm irradiation photodynamic therapy (PDT). Low pH hypoxia microenvironment (TME) activate nanocomposite release oxygen Ca . The released alleviate TME, thus enhancing efficiency COF-mediated PDT. Abundant were accumulated cells, resulting overload. Notably, reactive species (ROS) ensure sustained MPTP, change mitochondria transmembrane potential, cytochrome c (Cyt c) activation caspases apoptosis. Conclusion This multifunctional nanosystem TME responded abilities provided novel strategy innovative clinical therapy. Graphical

Language: Английский

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Mitochondrial Ca2+ Homeostasis: Emerging Roles and Clinical Significance in Cardiac Remodeling

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(6), P. 3025 - 3025

Published: March 11, 2022

Mitochondria are the sites of oxidative metabolism in eukaryotes where metabolites sugars, fats, and amino acids oxidized to harvest energy. Notably, mitochondria store Ca2+ work synergy with organelles such as endoplasmic reticulum extracellular matrix control dynamic balance concentration cells. vital heart tissue. Mitochondrial homeostasis is particularly important for maintaining physiological pathological mechanisms heart. plays a key role regulation cardiac energy metabolism, death, oxygen free radical production, autophagy. The imbalance mitochondrial closely associated remodeling. uniporter (mtCU) protein complex responsible uptake release consequently, This review summarizes remodeling regulatory effects calcium on cell autophagy, also provides theoretical basis novel target treatment cardiovascular diseases.

Language: Английский

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Heart failure with preserved ejection fraction (HFpEF) in type 2 diabetes mellitus: from pathophysiology to therapeutics

Journal of Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 14(5)

Published: April 29, 2022

Type 2 diabetes mellitus (T2DM or T2D) is a devastating metabolic abnormality featured by insulin resistance, hyperglycemia, and hyperlipidemia. T2D provokes unique changes compromises cardiovascular geometry function. Meanwhile, increases the overall risk for heart failure (HF) acts independent of classical factors including coronary artery disease, hypertension, valvular diseases. The incidence HF extremely high in patients with manifested as preserved, reduced, midrange ejection fraction (HFpEF, HFrEF, HFmrEF, respectively), all which significantly worsen prognosis T2D. HFpEF seen approximately half cases defined heterogenous syndrome discrete phenotypes, particularly close association syndrome. Nonetheless, management remains unclear, largely due to poorly pathophysiology behind HFpEF. Here, this review, we will summarize findings from multiple preclinical clinical studies well recent trials, mainly focusing on pathophysiology, potential mechanisms, therapies

Language: Английский

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Ginsenoside Rd promotes omentin secretion in adipose through TBK1-AMPK to improve mitochondrial biogenesis via WNT5A/Ca2+ pathways in heart failure

Redox Biology, Journal Year: 2023, Volume and Issue: 60, P. 102610 - 102610

Published: Jan. 14, 2023

Ginsenoside Rd is an active ingredient in Panax ginseng CA Mey and can be absorbed into the adipose tissue. Adipokines play important role treatment of cardiovascular diseases. However, potential benefit on heart failure (HF) underlying mechanism associated with crosstalk between adipocytes cardiomyocytes remains to illustrated. Here, results identified that improved cardiac function inhibited pathological changes transverse aortic constriction (TAC), coronary ligation (CAL) isoproterenol (ISO)-induced HF mice. And promoted release omentin from tissue up-regulated expression lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes. Further, could increase TBK1 AMPK phosphorylation also, TBK1-AMPK signaling pathway regulated LPS-induced Moreover, mRNA was significantly decreased by knockdown Additionally, molecular docking SPR analysis confirmed had a certain binding ability TBK1, co-treatment inhibitors or partially abolished effect increasing ratio p-AMPK we found circulating level diminished patients compared healthy subjects. Meanwhile, tissue-specific overexpression function, reduced myocardial infarct size ameliorated features CAL-induced Consistently, exogenous mtROS levels restored ΔψM improve oxygen glucose deprivation (OGD)-induced injury. WNT5A/Ca2+ mitochondrial biogenesis ameliorate ischemia WNT5A impairment counteracted cardioprotective vitro. Therefore, this study indicated secretion through via injury, which provided new therapeutic drugs for HF.

Language: Английский

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