Extracellular vesicles mediate biological information delivery: A double-edged sword in cardiac remodeling after myocardial infarction

Abstract

Acute myocardial infarction (AMI) is a severe ischemic disease with high morbidity and mortality worldwide. Maladaptive cardiac remodeling is a series of abnormalities in cardiac structure and function that occurs following myocardial infarction (MI). The pathophysiology of this process can be separated into two distinct phases: the initial inflammatory response, and the subsequent longer-term scar revision that includes the regression of inflammation, neovascularization, and fibrotic scar formation. Extracellular vesicles are nano-sized lipid bilayer vesicles released into the extracellular environment by eukaryotic cells, containing bioinformatic transmitters which are essential mediators of intercellular communication. EVs of different cellular origins play an essential role in cardiac remodeling after myocardial infarction. In this review, we first introduce the pathophysiology of post-infarction cardiac remodeling, as well as the biogenesis, classification, delivery, and functions of EVs. Then, we explore the dual role of these small molecule transmitters delivered by EVs in post-infarction cardiac remodeling, including the double-edged sword of pro-and anti-inflammation, and pro-and anti-fibrosis, which is significant for post-infarction cardiac repair. Finally, we discuss the pharmacological and engineered targeting of EVs for promoting heart repair after MI, thus revealing the potential value of targeted modulation of EVs and its use as a drug delivery vehicle in the therapeutic process of post-infarction cardiac remodeling.

Extracellular Vesicles’ Role in Angiogenesis and Altering Angiogenic Signaling

“…Furthermore, the study demonstrated the ability of MSC-secreted exosomes to mitigate ischemic–reperfusion injury of the myocardium by reducing the infarct size [ 113 , 114 , 115 ]. EVs originating from cardiac stem cells were also discovered to enhance cardiac function in an infarcted heart by reducing fibrosis, initiation angiogenesis, and stimulating the proliferation of cardiomyocytes [ 116 ].…”

“…Ischemic tissue injury is often treated by a skin flap transplantation, which relies heavily on promoting angiogenesis to ensure flap survival. The application of SC-derived exosomes led to a significant enhancement in the survival rate of these transplanted flaps while also increasing the activity of genes that promote the formation of new blood vessels [ 116 , 120 ]. In relation to addressing illnesses linked to malfunctioning vascular barriers, MSC-EVs have displayed potential in lessening pulmonary vascular permeability and lung damage during hemorrhagic shock [ 107 , 121 ].…”

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

“…Thus, blocking the generation and release of EVs was found to reduce blood pressure in hypertensive rats [ 203 ]. Furthermore, an increase in circulatory EC-EV levels has been found in patients with endothelial dysfunction [ 204 ], obstructive sleep apnea [ 205 ], obesity [ 206 , 207 ], renal failure [ 208 ], coronary artery disease [ 209 ], myocardial infarction [ 210 , 211 , 212 ], β-thalassemia [ 213 ], and stroke [ 214 ]. Nevertheless, it is not clear if the increase in their number contributes to these conditions.…”

Cell or cell derivative-laden hydrogels for myocardial infarction therapy: from the perspective of cell types

“…Different cells or cell-derived vesicles may have a dual function in early inflammation and late scar tissue formation in MI. 197 As a result, while administering cell or cell-inspired preparations, the antifibrotic or profibrotic effects must be considered. Furthermore, the feasibility of the mode of administration requires further investigation.…”