Hexarelin attenuates abdominal aortic aneurysm formation by inhibiting SMC phenotype switch and inflammasome activation

Bo Jiang; Mo Wang; Xue Li; Pengwei Ren; Guangxin Li; Yuqi Wang; Lei Wang; Xuan Li; Dong Yang; Lingfeng Qin; Shijie Xin

doi:10.1016/j.mvr.2021.104280

Hexarelin attenuates abdominal aortic aneurysm formation by inhibiting SMC phenotype switch and inflammasome activation

Microvasc Res. 2022 Mar:140:104280. doi: 10.1016/j.mvr.2021.104280. Epub 2021 Nov 29.

Authors

Bo Jiang¹, Mo Wang², Xue Li³, Pengwei Ren², Guangxin Li⁴, Yuqi Wang⁵, Lei Wang¹, Xuan Li¹, Dong Yang¹, Lingfeng Qin⁶, Shijie Xin⁷

Affiliations

¹ Department of Vascular Surgery, The First Hospital of China Medical University, Key Laboratory of Pathogenesis, Prevention and Therapeutics of Aortic Aneurysm, Shenyang, Liaoning 110001, China.
² Department of Surgery, Yale School of Medicine, New Haven, CT 06519, USA.
³ Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
⁴ Department of Breast and Thyroid Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, China.
⁵ Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
⁶ Department of Surgery, Yale School of Medicine, New Haven, CT 06519, USA. Electronic address: [email protected].
⁷ Department of Vascular Surgery, The First Hospital of China Medical University, Key Laboratory of Pathogenesis, Prevention and Therapeutics of Aortic Aneurysm, Shenyang, Liaoning 110001, China. Electronic address: [email protected].

PMID: 34856183
DOI: 10.1016/j.mvr.2021.104280

Abstract

Hexarelin, a synthetic growth hormone-releasing peptide, is shown to be protective in cardiovascular diseases such as myocardial infraction and atherosclerosis. However, the functional role of hexarelin in abdominal aortic aneurysm (AAA) remains undefined. The present study determined the effect of hexarelin administration (200 μg/kg twice per day) in a mouse model of elastase-induced abdominal aortic aneurysm. Echocardiography and in situ pictures showed hexarelin decreased infrarenal aorta diameter. Histology staining showed elastin degradation was improved in hexarelin-treated group. Hexarelin rescued smooth muscle cell contractile phenotype with increased α-SMA and decreased MMP2. Furthermore, hexarelin inhibited inflammatory cell infiltration, NLRP3 inflammasome activation and IL-18 production. Particularly, hexarelin suppressed NF-κB signaling pathway which is a key initiator of inflammatory response. These results demonstrated that hexarelin attenuated AAA development by inhibiting SMC phenotype switch and NF-κB signaling mediated inflammatory response.

Keywords: AAA; Hexarelin; Inflammasome; MMP; NF-κB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / pharmacology*
Aorta, Abdominal / drug effects
Aorta, Abdominal / immunology
Aorta, Abdominal / metabolism
Aorta, Abdominal / pathology
Aortic Aneurysm, Abdominal / immunology
Aortic Aneurysm, Abdominal / metabolism
Aortic Aneurysm, Abdominal / pathology
Aortic Aneurysm, Abdominal / prevention & control*
Cell Plasticity / drug effects*
Cytokines / metabolism
Disease Models, Animal
Inflammasomes / antagonists & inhibitors*
Inflammasomes / metabolism
Male
Mice
Mice, Inbred C57BL
Muscle, Smooth, Vascular / drug effects*
Muscle, Smooth, Vascular / immunology
Muscle, Smooth, Vascular / metabolism
Muscle, Smooth, Vascular / pathology
Myocytes, Smooth Muscle / drug effects*
Myocytes, Smooth Muscle / immunology
Myocytes, Smooth Muscle / metabolism
Myocytes, Smooth Muscle / pathology
NF-kappa B / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors*
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Oligopeptides / pharmacology*
Phenotype
Signal Transduction
Vascular Remodeling / drug effects

Substances

Anti-Inflammatory Agents
Cytokines
Inflammasomes
NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein
Nlrp3 protein, mouse
Oligopeptides
hexarelin