Potential Therapies to Protect the Aging Heart Against Ischemia/Reperfusion Injury

Díaz-Vesga, Magda C; Zúñiga-Cuevas, Úrsula; Ramírez-Reyes, Andrés; Herrera-Zelada, Nicolas; Palomo, Iván; Bravo-Sagua, Roberto; Riquelme, Jaime A.

doi:10.3389/fcvm.2021.770421

Cited by 5 publications

(4 citation statements)

References 74 publications

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“…Ageing represents one of the main risk factors for myocardial infarction and stroke. Both events initially cause hypoxia and ischaemia in the affected tissue, and later, if blood flow is restored, reperfusion injury occurs (Díaz‐Vesga et al, 2021; Kalaria et al, 2016). Fas levels were higher in the brains of old rats after one hour of hypoxia and two hours of reoxygenation than in young rats.…”

Section: Changes In the Fas/fasl System In Age‐related Processes And ...mentioning

confidence: 99%

Fas (CD95)/FasL (CD178) system during ageing

Lagunas‐Rangel

2023

Cell Biology International

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The Fas/FasL system plays a central role in the physiological regulation of apoptosis and has been implicated in the pathogenesis of several neoplasms and diseases of the immune system. Until now, it has received little attention in the context of ageing, but there is sufficient evidence that it plays an important role in this process and its deregulation favours the development of age‐related diseases such as osteoarthritis, diabetes, eye diseases, ischaemic processes, anaemia, Alzheimer's disease and cancer. With this in mind, the aim of this work was to describe the main changes that occur in the Fas/FasL system during ageing and their association with the development of age‐related diseases. Furthermore, it discusses how exercise and diet, considered the cornerstone of almost all healthy ageing programmes, produce beneficial effects through the regulation of the Fas/FasL system.

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Section: Changes In the Fas/fasl System In Age‐related Processes And ...mentioning

confidence: 99%

Fas (CD95)/FasL (CD178) system during ageing

Lagunas‐Rangel

2023

Cell Biology International

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“…The anti-aging drug dasatinib combined with quercetin has shown an excellent protective effect in patients with idiopathic pulmonary fibrosis and diabetic nephropathy. Whether connecting the two drugs can translate into cardioprotection in the elderly requires more preclinical evidence ( 148 ).…”

Section: Multi-target Strategies For Myocardial Ischemia-reperfusion ...mentioning

confidence: 99%

“…Meanwhile, most experiments focus on isolated hearts and small animal models such as mice, rats, and rabbits. Large animal models (such as pigs) are rarely studied due to the complexity of experimental design, experimental conditions, research costs, and experimental regulatory requirements ( 130 , 131 , 141 , 144 , 148 ). Exenatide and RIC exert additive effects on cardioprotection in porcine myocardial IRI by activating distinct cardioprotective pathways, which looks very attractive for clinical translation ( 152 ).…”

Section: Clinical Translation Of Multi-target Strategies For Myocardi...mentioning

confidence: 99%

Preclinical multi-target strategies for myocardial ischemia-reperfusion injury

Gao

2022

Front. Cardiovasc. Med.

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Despite promising breakthroughs in diagnosing and treating acute coronary syndromes, cardiovascular disease’s high global mortality rate remains indisputable. Nearly half of these patients died of ischemic heart disease. Primary percutaneous coronary intervention (PCI) and coronary artery bypass grafting can rapidly restore interrupted blood flow and become the most effective method for salvaging viable myocardium. However, restoring blood flow could increase the risk of other complications and myocardial cell death attributed to myocardial ischemia-reperfusion injury (IRI). How to reduce the damage of blood reperfusion to ischemic myocardium has become an urgent problem to be solved. In preclinical experiments, many treatments have substantial cardioprotective effects against myocardial IRI. However, the transition from these cardioprotective therapies to clinically beneficial therapies for patients with acute myocardial infarction remains elusive. The reasons for the failure of the clinical translation may be multi-faceted, and three points are summarized here: (1) Our understanding of the complex pathophysiological mechanisms of myocardial IRI is far from enough, and the classification of specific therapeutic targets is not rigorous, and not clear enough; (2) Most of the clinical patients have comorbidities, and single cardioprotective strategies including ischemia regulation strategies cannot exert their due cardioprotective effects under conditions of hyperglycemia, hypertension, hyperlipidemia, and aging; (3) Most preclinical experimental results are based on adult, healthy animal models. However, most clinical patients had comorbidities and received multiple drug treatments before reperfusion therapy. In 2019, COST Action proposed a multi-target drug combination initiative for prospective myocardial IRI; the optimal cardioprotective strategy may be a combination of additive or synergistic multi-target therapy, which we support. By establishing more reasonable preclinical models, screening multi-target drug combinations more in line with clinical practice will benefit the translation of clinical treatment strategies.

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“…Cardiovascular diseases are the leading cause of death worldwide, taking more than 17.9 million lives each year (one-third of all deaths worldwide), with more than four out of five deaths due to heart attack or stroke [ 1 ]. Despite reduced mortality due to important advances in the treatment of myocardial infarction (therapeutic targets, peptides, drugs), there is a need to limit the extent of infarct size after reperfusion injury, thus preventing the onset and severity of heart failure [ 2 ]. The role of age in tolerance to ischemic injury has been studied for several decades, but the results are controversial [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Changes in Calcium Regulation after Myocardial Ischemia–Reperfusion Injury

et al. 2023

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During aging, heart structure and function gradually deteriorate, which subsequently increases susceptibility to ischemia–reperfusion (IR). Maintenance of Ca2+ homeostasis is critical for cardiac contractility. We used Langendorff’s model to monitor the susceptibility of aging (6-, 15-, and 24-month-old) hearts to IR, with a specific focus on Ca2+-handling proteins. IR, but not aging itself, triggered left ventricular changes when the maximum rate of pressure development decreased in 24-month-olds, and the maximum rate of relaxation was most affected in 6-month-old hearts. Aging caused a deprivation of Ca2+-ATPase (SERCA2a), Na+/Ca2+ exchanger, mitochondrial Ca2+ uniporter, and ryanodine receptor contents. IR-induced damage to ryanodine receptor stimulates Ca2+ leakage in 6-month-old hearts and elevated phospholamban (PLN)-to-SERCA2a ratio can slow down Ca2+ reuptake seen at 2–5 μM Ca2+. Total and monomeric PLN mirrored the response of overexpressed SERCA2a after IR in 24-month-old hearts, resulting in stable Ca2+-ATPase activity. Upregulated PLN accelerated inhibition of Ca2+-ATPase activity at low free Ca2+ in 15-month-old after IR, and reduced SERCA2a content subsequently impairs the Ca2+-sequestering capacity. In conclusion, our study suggests that aging is associated with a significant decrease in the abundance and function of Ca2+-handling proteins. However, the IR-induced damage was not increased during aging.

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Potential Therapies to Protect the Aging Heart Against Ischemia/Reperfusion Injury

Cited by 5 publications

References 74 publications

Fas (CD95)/FasL (CD178) system during ageing

Fas (CD95)/FasL (CD178) system during ageing

Preclinical multi-target strategies for myocardial ischemia-reperfusion injury

Age-Dependent Changes in Calcium Regulation after Myocardial Ischemia–Reperfusion Injury

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