Signaling pathways and targeted therapy for myocardial infarction

Abstract

Although the treatment of myocardial infarction (MI) has improved considerably, it is still a worldwide disease with high morbidity and high mortality. Whilst there is still a long way to go for discovering ideal treatments, therapeutic strategies committed to cardioprotection and cardiac repair following cardiac ischemia are emerging. Evidence of pathological characteristics in MI illustrates cell signaling pathways that participate in the survival, proliferation, apoptosis, autophagy of cardiomyocytes, endothelial cells, fibroblasts, monocytes, and stem cells. These signaling pathways include the key players in inflammation response, e.g., NLRP3/caspase-1 and TLR4/MyD88/NF-κB; the crucial mediators in oxidative stress and apoptosis, for instance, Notch, Hippo/YAP, RhoA/ROCK, Nrf2/HO-1, and Sonic hedgehog; the controller of myocardial fibrosis such as TGF-β/SMADs and Wnt/β-catenin; and the main regulator of angiogenesis, PI3K/Akt, MAPK, JAK/STAT, Sonic hedgehog, etc. Since signaling pathways play an important role in administering the process of MI, aiming at targeting these aberrant signaling pathways and improving the pathological manifestations in MI is indispensable and promising. Hence, drug therapy, gene therapy, protein therapy, cell therapy, and exosome therapy have been emerging and are known as novel therapies. In this review, we summarize the therapeutic strategies for MI by regulating these associated pathways, which contribute to inhibiting cardiomyocytes death, attenuating inflammation, enhancing angiogenesis, etc. so as to repair and re-functionalize damaged hearts.

Notoginsenoside R1-loaded mesoporous silica nanoparticles targeting the site of injury through inflammatory cells improves heart repair after myocardial infarction

“…It has been reported that calcitonin gene-related peptide regulated cardiomyocyte survival through regulation of oxidative stress by PI3K/Akt and MAPK signaling pathways [ 66 ]. Hippo/YAP is one of the crucial mediators in oxidative stress and apoptosis after MI [ 67 ]. It was reported that Hippo-YAP signaling modulated the FoxO1-mediated antioxidant response in the setting of I/R in the heart [ 68 ].…”

Uncovering the Effect and Mechanism of Rhizoma Corydalis on Myocardial Infarction Through an Integrated Network Pharmacology Approach and Experimental Verification

“…We also constructed a component-core target network and found that 60 bioactive components regulated 12 core targets, including AR, ESR1, CDK2, HSP90AA1, HSPA8, EGFR, AKT1, PARP1, GRB2, MDM2, HSP90AB1, and HSPA1A, which are closely involved in the apoptotic process (Figure 3; Supplementary Table S3). Apoptosis, which can be triggered by MI, is an energy-dependent programmed process responsible for cell removal (Zhang et al, 2022). Mitochondrial dysfunction is an important part of apoptosis caused by MI and is related to the impaired permeability of the mitochondrial outer membrane, causing the release of apoptosisrelated proteins, such as apoptosis-inducing factor, Bcl-2 proteins, and cytochrome c (Ong and Gustafsson, 2012;Del Re et al, 2019).…”

Atrial myocytes-derived exosomal microRNA contributes to atrial fibrosis in atrial fibrillation

“…In addition, studies also show that CTGF activates PI3K and AKT pathway, contributing to inhibition of GPD1L expression and promoting angiogenesis in human synovial broblasts [36] . Zhang et al found that principal signaling pathways of PI3K/Akt, TGF-β/SMADs, Wnt/β-catenin, and NLRP3/caspase-1, which mainly centered on various pathological states such as in ammation, oxidative stress, brosis, hypertrophy, apoptosis, and regeneration post MI [37] . Up-regulated PI3K and phosphorylation of AKT could involve in the enhancement of proliferation and migration capabilities of cardiac broblasts, which could be reversed by PI3K inhibitor [38] .…”