RESUMO

This study investigated the role of Poly (ADP-ribose) Polymerase (PARP) in myocardial ischemia-reperfusion injury (MIRI) in elderly mice. It involves 30 elderly male KM mice divided into three groups: Sham, MIRI, and DPQ, where the MIRI and DPQ groups undergo myocardial ischemia-reperfusion with the DPQ group also receiving DPQ for PARP-1 inhibition. Over three weeks, assessments include histological analysis of myocardial lesions, left ventricular ejection fraction (LVEF) measurements, and evaluations of serum cardiac enzymes and inflammatory markers. This approach aims to understand the protective effects of DPQ in MIRI, focusing on its impact on cardiac health and inflammation via the JAK2/STAT3 pathway. The findings suggest that PARP activation exacerbates cardiac dysfunction and inflammation in MIRI by possibly modulating the JAK2/STAT3 signaling pathway. Inhibition of PARP-1 with DPQ mitigates these effects, as indicated by reduced myocardial lesions and inflammatory infiltration, improved LVEF, and altered levels of inflammatory markers and signaling molecules. However, the differences in STAT3 and p-STAT3 protein expression between the DPQ and MIRI groups were not statistically significant, suggesting that while PARP inhibition affects many aspects of MIRI pathology, its impact on the JAK2/STAT3 pathway may not fully explain the observed benefits. This study contributes to our understanding of the complex mechanisms underlying myocardial ischemia-reperfusion injury, particularly in the context of aging. It highlights the potential of PARP inhibition as a therapeutic strategy to attenuate cardiac dysfunction and inflammation in MIRI, though further research is necessary to fully elucidate the underlying molecular pathways and to explore the clinical relevance of these findings in humans.

Assuntos

Janus Quinase 2 , Traumatismo por Reperfusão Miocárdica , Miocárdio , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Masculino , Camundongos , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Miocárdio/patologia , Miocárdio/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Envelhecimento , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos

RESUMO

Background and Purpose: Multiple guidelines suggest the ω-3 polyunsaturated fatty acids (ω-3 PUFAs) help to prevent major vascular events of coronary heart disease (CHD), but the data on large trials of ω-3 fatty acids are controversial. We reviewed the available evidence to determine the effect of ω-3 PUFAs on coronary atherosclerosis. Materials and Methods: Literature were from online databases. Randomized controlled trials (RCTs) or observational studies were acceptable. Quantitative data synthesis was conducted using R version 4.1.2. Each outcome was calculated using standardized mean difference (SMD) in a random-effect model. Sensitivity analysis was conducted for each outcome. A total of 21 RCTs and 1 observational study with 2,277 participants were included. Results: Meta-analysis indicated a benefit of ω-3 PUFAs on coronary atherosclerosis, namely, (1) ω-3 PUFAs can reduce the atherosclerotic plaque volume (SMD -0.18; 95% CI -0.31 to -0.05); (2) ω-3 PUFAs can help reduce the loss of the diameter of the narrowest segments of coronary arteries in patients with CHD (SMD 0.29; 95% CI, 0.05-0.53); (3) ω-3 PUFAs do not have significant effect on volume of lipid plaque in coronary arteries (SMD -1.18; 95% CI -2.95 to 0.58), volume of fiber plaque (SMD 0.26; 95% CI -0.81 to 1.33), and calcified plaque (SMD 0.17; 95% CI -0.55 to 0.89); and (4) ω-3 PUFAs had no significant effect on endothelial inflammatory factors in peripheral blood. Conclusions: We confirmed that ω-3 PUFAs benefit patients with CHD by reducing the progression of coronary atherosclerosis. We indicated that the benefits were not caused by reducing endothelial inflammations of coronary arteries. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021285139, identifier: CRD42021285139.