The ACE2-Ang (1–7)-Mas receptor axis attenuates cardiac remodeling and fibrosis in post-myocardial infarction

Abstract

Myocardial remodeling serves an important role in the pathophysiology of coronary heart disease. The angiotensin-converting enzyme (ACE)2-angiotensin-(1–7) [Ang (1–7)]-Mas receptor (MasR) axis is a key regulator in myocardial remodeling and development of heart failure. To investigate how ACE2-Ang-(1–7)-MasR axis function on myocardial remodeling and cardiac fibrosis in post-myocardial infarction (MI), male Sprague-Dawley rats (weight, 200±20 g) were used to establish the model of myocardial infarction by ligating the left coronary artery. The present study suggests that telmisartan (Tel) and olmesartan (Olm) (5 mg/kg/d) can inhibit myocardial remodeling of post-myocardial infarction through the ACE2-Ang (1–7)-MasR pathway. Administration of Tel or Olm was demonstrated to significantly inhibit collagen deposition using Masson staining. In addition, telmisartan and olmesartan was indicated to antagonize angiotensin II (Ang II) and upregulate ACE2, MasR, Ang (1–7) expression in myocardial tissue using immunoassay and ELISA test, and the effect of Olm was more marked than that of Tel at the same dosage. Simultaneously, compared with the MI or Sham group, the mRNA and protein expression of ACE2, Ang II and MasR in myocardial tissue demonstrated a remarkable increase in the Olm group, when compared with the Tel group. Taken together, our data demonstrated that ACE2-Ang (1–7)-MasR axis may present a potential protective role in the development of myocardial remodeling and may provide a new target for drug development of cardiac fibrosis. In conclusion, Olm is superior to Tel in inhibiting myocardial local Ang II level reducing myocardial collagen deposition and improving myocardial remodeling by upregulating the expression of ACE2, Ang (1–7) and MasR.

Relationship between circulating levels of angiotensin-converting enzyme 2-angiotensin-(1–7)-MAS axis and coronary heart disease

“…As is mentioned above, Ang-(1-7) and Ang-(1-9) have been proposed to be important mediators in cardioprotection [51]. A series of studies demonstrated that both plasma and myocardial tissue levels of Ang-(1-7) significantly increased in myocardial infarction [41,52]. In contrast, another study indicated that the circulating levels of Ang-(1-9), but not Ang-(1-7) levels, increased 1 week after myocardial infarction [38].…”

Clinical Implications of SARS-CoV-2 Interaction With Renin Angiotensin System

“…A recent study in the same murine model demonstrated that treatment with olmesartan or telmisartan increased both cardiac ACE2 mRNA and protein expression while augmenting plasma Ang 1-7/Ang II ratios resulting in improved cardiac function and alleviated collagen disposition [40]. These experiments suggest that both ACE inhibitors and ARBs variably upregulated ACE2 expression [50]. ARBs inhibit binding of Ang II to AT1 receptor, permitting circulating Ang II to be shunted to ACE2 for conversion to Ang1-7.…”

Coronavirus 2019 Infection in People with Associated Co-Morbidities: Case Fatality and ACE2 Inhibitors Treatment Concerns

“…RAAS is also up-regulated in diabetes leading to activation of AngII pathway and subsequently inflammation, increased oxidative stress, cell proliferation as well as apoptosis, and fibrosis which contribute to cardiac remodeling and atherosclerosis. While, ACE2 improves cardiac function by preventing myocardial fibrosis, reducing remodeling and the development of left ventricular hypertrophy as well as pressure-overload-induced heart failure [21].Therefore, RAAS inhibition by ACE inhibitors and angiotensin II receptor blockers has been recommended as the first line therapy in CVD in people with diabetes by lowering target-organ damageas well…”