Effect of Neprilysin Inhibition for Ischemic Mitral Regurgitation after Myocardial Injury

Autor: Jong-Min Song, Eunhye Ji, Naaleum Song, Sahmin Lee, Kyoung-Hee Choi, Hyo-Sook Hwang, Geun-Hyung Kang, Duk-Hyun Kang
Rok vydání: 2021
Předmět:
Male
Angiotensin receptor
Myocardial Infarction
heart failure
Ventricular Function
Left
Rats
Sprague-Dawley
Fibrosis
Occlusion
Medicine
Biology (General)
Neprilysin
Cells
Cultured
Spectroscopy
mitral valve insufficiency
Ventricular Remodeling
Aminobutyrates
General Medicine
Computer Science Applications
Chemistry
Drug Combinations
medicine.anatomical_structure
Valsartan
Cardiology
Mitral Valve
medicine.drug
medicine.medical_specialty
QH301-705.5
Myocardial Reperfusion Injury
Article
Catalysis
neprilysin
Inorganic Chemistry
Internal medicine
angiotensin receptor antagonists
Animals
Humans
cardiovascular diseases
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
business.industry
Biphenyl Compounds
Organic Chemistry
Endothelial Cells
heart ventricles
medicine.disease
Rats
Ventricle
Heart failure
business
Corn oil
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 16
International Journal of Molecular Sciences, Vol 22, Iss 8598, p 8598 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22168598
Popis: Angiotensin receptor neprilysin inhibitor (ARNI) treatment reduces functional mitral regurgitation (MR) to a greater extent than angiotensin receptor blocker (ARB) treatment alone, but the mechanism is unclear. We evaluated the mechanisms of how ARNI has an effect on functional MR. After inducing functional MR by left circumflex coronary artery occlusion, male Sprague Dawley rats (n = 31) were randomly assigned to receive the ARNI LCZ696, the ARB valsartan, or corn oil only (MR control). Excised mitral leaflets and left ventricle (LV) were analyzed, and valvular endothelial cells were evaluated focusing on molecular changes. LCZ696 significantly attenuated LV dilatation after 6 weeks when compared with the control group (LV end-diastolic volume, 461.3 ± 13.8 µL versus 525.1 ± 23.6 µL
p <
0.05), while valsartan did not (471.2 ± 8.9 µL
p >
0.05 to control). Histopathological analysis of mitral leaflets showed that LCZ696 strongly reduced fibrotic thickness compared to the control group (28.2 ± 2.7 µm vs. 48.8 ± 7.5 µm
0.05). Transforming growth factor-β and downstream phosphorylated extracellular-signal regulated kinase were also significantly lower in the LCZ696 group. Consequently, excessive endothelial-to-mesenchymal transition (EndoMT) was mitigated in the LCZ696 group compared to the control group and leaflet area was higher (11%) in the LCZ696 group than in the valsartan group. Finally, the MR extent was significantly lower in the LCZ696 group and functional improvement was observed. In conclusion, neprilysin inhibitor has positive effects on LV reverse remodeling and also attenuates fibrosis in MV leaflets and restores adaptive growth by directly modulating EndoMT.
Databáze: OpenAIRE
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