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Background: Sacubitril/Valsartan, a dual inhibitor of the neprilysin and angiotensin receptor, exerts cardioprotective effects in heart failure. Little is known on the impact of Sacubitril/Valsartan in hypertensive patients early post myocardial infarction., Methods: Spontaneously hypertensive rats (SHR) were pretreated by daily angiotensin receptor blocker (ARB; 30 mg/kg intraperitoneally), Sacubitril/Valsartan (ARNI; 60 mg/kg intraperitoneally) or the same dosage of physiological saline for 1 week. Then each group underwent myocardial infarction induction and received the same treatment for another week. The blood pressure and cardiac function were evaluated prior to sacrifice. We performed histological and molecular evaluation of fibrosis in vivo and in vitro., Results: The blood pressure was comparable between three groups both 1 week prior to and post myocardial infarction. ARNI and ARB restore the decreased ejection fraction (57.3 ± 7.6 vs. 42.9 ± 5.2%, P < 0.05; 54.3 ± 6.9 vs. 42.9 ± 5.2%, P < 0.01, respectively) and fractional shortening (31.6 ± 5.4 vs. 22.1 ± 3.1%, P < 0.05; 29.4 ± 4.5 vs. 22.1 ± 3.1%, P < 0.05, respectively) post myocardial infarction. The infarct size and collagen deposition were also significantly mitigated in ARNI and ARB groups. In addition, ARNI and ARB treatment reduced the expression of cardiac remodeling-related factors, such as Bnp, α-SMA, Vimentin, and Col1a1 (all P < 0.05 vs. MI group). Finally, ARNI and ARB decreased the expression of α-SMA in cardiac fibroblasts treated with Ang II., Conclusion: In conclusion, pretreatment with ARNI maintained cardiac function and reduced myocardial fibrosis in myocardial infarction, probably prior to any anti-hypertensive effect., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been confirmed to reduce the rate of rehospitalization for heart failure and cardiovascular death in diabetic patients. The aim of our study was to investigate the cardioprotective role of SGLT2 inhibitors in early myocardial infarction (MI) of non-diabetic mice., Methods: C57BL/6 mice underwent left artery coronary artery descending (LAD) ligation to induce MI. Following the surgery, animals were randomized to receive saline or empagliflozin. Empagliflozin (EMPA) was administrated at 10 mg/kg per day by oral gavage for 2 weeks. Echocardiography, histological staining and qualitative RT-PCR were performed to assess the cardiac remodeling post MI. In vitro experiments were performed to evaluate the effect of empagliflozin on apoptosis, oxidative stress and mitochondrial membrane potential of cardiomyocyte subjected to hypoxic treatment., Results: Compared with MI group, the empagliflozin treatment group showed improved cardiac function, reduced infarct size and interstitial fibrosis. Empagliflozin also inhibited cardiomyocyte apoptosis by alleviating oxidative stress and restoring mitochondrial membrane potential. Immunoblotting analysis revealed activated AMP-activated protein kinase (AMPK) signaling may mediated the cardioprotective role of empagliflozin., Conclusions: In summary, empagliflozin could inhibit cardiomyocyte apoptosis and improve cardiac remodeling early MI, which provided insights into the benefic effect of empagliflozin on MI patients without diabetes., (Copyright © 2021. Published by Elsevier B.V.)

The cardiac repair after myocardial infarction (MI) involves two phases, namely, inflammatory response and proliferative response. The former is an inflammatory reaction, evoked by different kinds of pro-inflammatory leukocytes and molecules stimulated by myocardial necrosis, while the latter is a repair process, predominated by a magnitude of anti-inflammatory cells and cytokines, as well as fibroblasts. Cardiac remodeling post-MI is dependent on the balance of individualized intensity of the post-MI inflammation and subsequent cardiac fibrosis. During the past 30 years, enormous studies have focused on investigating immune cells and mediators involved in cardiac inflammation and fibrosis, which are two interacting processes of post-MI cardiac repair. These results contribute to revealing the mechanism of adverse cardiac remodeling after MI and alleviating the impairment of cardiac function. In this study, we will broadly discuss the role of immune cell subpopulation and the involved cytokines and chemokines during cardiac repair post-MI, particular in cardiac inflammation and fibrosis., (© 2020 Wiley Periodicals, Inc.)

Background: The angiogenesis post myocardial infarction (MI) is compromised in diabetes. MiR-144-3p is reported to be highly expressed in circulating exosomes of diabetic patients, implying its role in diabetic complications. However, whether circulating exosomes and enriched miR-144-3p are involved in the impaired neovascularization in diabetes and the underlying mechanism is unclear., Results: DMexo and miR-144-3p mimic-treated MSCs had elevated miR-144-3p levels and decreased MMP9, Ets1 and PLG expression. The percentage of EPCs were relatively lower in DMexo-treated or agomir-treated MI mice compared with MI mice. Finally, the luciferase assay confirmed the direct binding between miR-144-3p and Ets1., Conclusion: Exosomal miR-144-3p could impair the mobilization ability of EPCs, which was associated with impaired ischemia-induced neovascularization., Methods: Circulating exosomes were isolated from Streptozotocin (STZ)-induced mice. In vitro , mesenchymal stem cells (MSCs) were incubated with exosomes from diabetic mice (DMexo), and miR-144-3p mimic or inhibitor. miR-144-3p, and MMP9 pathway were measured using qPCR and immunoblotting. In vivo , MI mice induced by left anterior descending ligation were treated with DMexo, as well as miR-144-3p agomir. Flow cytometry was used to profile endothelial progenitor cells (EPCs) in peripheral blood and bone marrow post 24 hours respectively.

The inflammation modulation effects of mesenchymal stromal cell-derived exosomes (MSC-EXO) are well established. We aimed to explore the mechanism behind the inflammatory responses of numerous exosomal cargo molecules that have been neglected in molecular biology research, and to develop an exosomal cargo delivery system that can exert a stronger therapeutic effect on myocardial ischemia-reperfusion (I/R) injury. Computational approaches were used to identify key exosomal miRNAs and their downstream mRNAs that are expressed in the inflammatory response. Direct interactions between miRNA-181a and the c-Fos mRNA complex were confirmed by luciferase reporter assay. MSC-EXO carrying miRNA-181a-overexpressing lentiviruses were intramyocardially injected into a mouse model of myocardial I/R injury. I/R progression was evaluated through echocardiography and immunofluorescence microscopy. miRNA-181a provided substantial coverage against a host of immune-related genes through the miRNA-mRNA network. miRNA-181a delivery by MSC-EXO combined the immune-suppressing effect of miRNA-181a and the cell targeting capability of MSC-EXO to exert a stronger therapeutic effect on myocardium I/R injury. We showed the potential of MSC-EXO as a tool for the specific delivery of small RNAs in vivo. This study shed new light on the potential application of miRNA-181a-overexpressing MSC-EXO as a therapeutic strategy for myocardial I/R injury. [ABSTRACT FROM AUTHOR]