Benazepril improves myocardial remodeling after myocardial infarction by down-regulating cardiac ankyrin repeat protein

doi:10.3877/cma.j.issn.1674-6880.2023.04.005

Abstract

Abstract:

Objective

To investigate the relationship between the improvement of myocardial remodeling by Benazepril and the expression of cardiac ankyrin repeat protein (CARP) after myocardial infarction in rats.

Methods

A total of 70 Sprague-Dawley rats were randomly divided into a sham surgery group (n = 20), a myocardial infarction group (n = 25) and a Benazepril group (n = 25). Eight rats were included at 7 days and 28 days after surgery in each group using random number tables. Rats in the myocardial infarction group and Benazepril group were induced by ligating the anterior descending coronary artery, while rats in the sham surgery group were anesthetized with thoracotomy and threaded without ligation. In the Benazepril group, 10 mg·kg^-1·d^-1 Benazepril (dissolved in 5 mL/kg isotonic sodium chloride solution) was used for gavage. Rats in the sham surgery group and myocardial infarction group were treated with 10 mg·kg^-1·d^-1 isotonic sodium chloride solution. After feeding for 7 days and 28 days, the hearts were removed after the rats were sacrificed, and the left ventricular weight index (LVWI) and cardiomyocyte cross-sectional area were determined. The characteristics of myocardial histopathology were observed by hematoxylin-eosin (HE) staining, and the expression levels of CARP and angiotensin Ⅱ (AngⅡ) in the serum and cardiac myocytes were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry respectively.

Results

HE staining showed that at 7 days and 28 days after surgery, the myocardial structures of rats in the sham surgery group were intact, the cells were neatly arranged, and the nuclei were located in the center of the cells, with uniform staining and no myofilament break. In the myocardial infarction group, cardiomyocytes were severely degenerated and necrotic in the infarct area with disordered myofilament arrangement, inflammatory cell infiltration and massive collagen fiber hyperplasia, and cardiomyocytes were compensatorily hypertrophied in the non-infarcted area. Rats in the Benazepril group had milder cardiomyocyte lesions and less inflammatory cell infiltration. Myocardial fibrosis in the infarct zone was more obvious in the myocardial infarction group and Benazepril group at 28 days than at 7 days after surgery. After 7 days and 28 days postoperatively, the levels of LVWI (F = 25.111, P < 0.001), cardiomyocyte cross-sectional area (F = 566.062, P < 0.001), and CARP (F = 90.384, 23.642; both P < 0.001) and AngⅡ (F = 97.764, 116.133; both P < 0.001) in serum and cardiomyocytes were compared among the three groups, and the differences were statistically significant. After 28 days after surgery, the levels of cardiomyocyte cross-sectional area, serum CARP and AngⅡ, and cardiomyocyte AngⅡ in the myocardial infarction group were significantly higher than those in the sham surgery group and Benazepril group (all P < 0.05). The immunohistochemistry showed that CARP and AngⅡ were mainly expressed in the cytoplasm. In the sham surgery group, the myocardial cells were lighter in yellow and brown, and the positive rates of CARP and AngⅡ were lower. Rats in the myocardial infarction group were covered with cloth yellow and brown granules and had higher positive expression. The positive expression rate in the Benazepril group was intermediate between the sham surgery and myocardial infarction groups. In addition, the expression levels of CARP and AngⅡ in cardiomyocytes at 7 days in the myocardial infarction group and Benazepril group were higher than those at 28 days. Pearson correlation analysis showed that there were positive correlations between CARP and AngⅡ in serum (r = 0.796, 0.894; both P < 0.001) and myocardium (r = 0.880, 0.807; both P < 0.001) at 7 days and 28 days postoperatively.

Conclusions

After myocardial infarction, CARP and AngⅡ are significantly elevated in serum and myocardial tissue and both are involved in its myocardial remodeling, and there is a positive correlation between them. Improvement of myocardial remodeling after myocardial infarction by Benazepril may be related to the down-regulation of CARP.

Key words: Cardiac ankyrin repeat protein, Angiotensin Ⅱ, Myocardial infarction, Cardial remodeling

Yixue Zhang, Moshui Chen, Fuwei Zhang, Ying Zheng, Dingjun Sun, Qingfei Ye. Benazepril improves myocardial remodeling after myocardial infarction by down-regulating cardiac ankyrin repeat protein[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2023, 16(04): 292-299.

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References 20

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组别	只数	LVWI（mg/g）		心肌细胞横截面积（× 10⁴ μm²）
组别	只数	7 d	28 d	7 d	28 d
假手术组	8	2.34 ± 0.09	2.30 ± 0.10	13.3 ± 0.7	14.6 ± 0.8
心肌梗死组	8	2.96 ± 0.15^a	3.13 ± 0.18^a	32.8 ± 1.0^a	28.8 ± 1.0^a
贝那普利组	8	2.64 ± 0.62^a	2.81 ± 0.30^a	18.7 ± 1.1^ab	21.9 ± 0.8^ab
F值		25.111		566.062
P值		<0.001		<0.001

组别	只数	LVWI（mg/g）		心肌细胞横截面积（× 10⁴ μm²）
组别	只数	7 d	28 d	7 d	28 d
假手术组	8	2.34 ± 0.09	2.30 ± 0.10	13.3 ± 0.7	14.6 ± 0.8
心肌梗死组	8	2.96 ± 0.15^a	3.13 ± 0.18^a	32.8 ± 1.0^a	28.8 ± 1.0^a
贝那普利组	8	2.64 ± 0.62^a	2.81 ± 0.30^a	18.7 ± 1.1^ab	21.9 ± 0.8^ab
F值		25.111		566.062
P值		<0.001		<0.001

组别	只数	CARP（ng/L）		AngⅡ（ng/L）
组别	只数	7 d	28 d	7 d	28 d
假手术组	8	15.4 ± 3.0	14.2 ± 1.2	11.1 ± 1.3	8.7 ± 0.9
心肌梗死组	8	34.0 ± 3.5^a	26.6 ± 1.1^a	21.2 ± 1.7^a	17.0 ± 0.7^a
贝那普利组	8	21.7 ± 1.9^b	18.4 ± 1.6^ab	15.0 ± 1.5^ab	13.9 ± 1.0^ab
F值		90.384		97.764
P值		<0.001		<0.001

组别	只数	CARP（ng/L）		AngⅡ（ng/L）
组别	只数	7 d	28 d	7 d	28 d
假手术组	8	15.4 ± 3.0	14.2 ± 1.2	11.1 ± 1.3	8.7 ± 0.9
心肌梗死组	8	34.0 ± 3.5^a	26.6 ± 1.1^a	21.2 ± 1.7^a	17.0 ± 0.7^a
贝那普利组	8	21.7 ± 1.9^b	18.4 ± 1.6^ab	15.0 ± 1.5^ab	13.9 ± 1.0^ab
F值		90.384		97.764
P值		<0.001		<0.001

组别	只数	CARP（ng/L）		AngⅡ（ng/L）
组别	只数	7 d	28 d	7 d	28 d
假手术组	8	0.057 ± 0.011	0.058 ± 0.011	0.215 ± 0.021	0.179 ± 0.031
心肌梗死组	8	0.117 ± 0.022^a	0.107 ± 0.017^a	1.232 ± 0.117^a	1.173 ± 0.210^a
贝那普利组	8	0.082 ± 0.011^ab	0.075 ± 0.011^b	0.544 ± 0.058^ab	0.495 ± 0.158^ab
F值		23.642		116.133
P值		<0.001		<0.001

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