Peri-Adventitial Delivery of Smooth Muscle Cells in Porous Collagen Scaffolds for Treatment of Experimental Abdominal Aortic Aneurysm

2021 ◽  
Author(s):  
Joscha Mulorz ◽  
Mahdis Shayan ◽  
Caroline Hu ◽  
Cynthia Alcazar ◽  
Alex H.P Chan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vessel Wall ◽  
Muscle Cells ◽  
Collagen Scaffolds ◽  
Abdominal Aortic ◽  
Direct Delivery

Abdominal aortic aneurysm (AAA) is associated with the loss of vascular smooth muscle cells (SMCs) within the vessel wall. Direct delivery of therapeutic cells is challenging due to impaired mechanical...

scholarly journals Vascular Smooth Muscle Cells in Aortic Aneurysm: From Genetics to Mechanisms

2021 ◽  
Author(s):  
Haocheng Lu ◽  
Wa Du ◽  
Lu Ren ◽  
Milton H. Hamblin ◽  
Richard C. Becker ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Thoracic Aortic Aneurysm ◽  
Muscle Cells ◽  
Abdominal Aortic ◽  
Aneurysm Development

Abstract Aortic aneurysm, including thoracic aortic aneurysm and abdominal aortic aneurysm, is the second most prevalent aortic disease following atherosclerosis, representing the ninth‐leading cause of death globally. Open surgery and endovascular procedures are the major treatments for aortic aneurysm. Typically, thoracic aortic aneurysm has a more robust genetic background than abdominal aortic aneurysm. Abdominal aortic aneurysm shares many features with thoracic aortic aneurysm, including loss of vascular smooth muscle cells (VSMCs), extracellular matrix degradation and inflammation. Although there are limitations to perfectly recapitulating all features of human aortic aneurysm, experimental models provide valuable tools to understand the molecular mechanisms and test novel therapies before human clinical trials. Among the cell types involved in aortic aneurysm development, VSMC dysfunction correlates with loss of aortic wall structural integrity. Here, we discuss the role of VSMCs in aortic aneurysm development. The loss of VSMCs, VSMC phenotypic switching, secretion of inflammatory cytokines, increased matrix metalloproteinase activity, elevated reactive oxygen species, defective autophagy, and increased senescence contribute to aortic aneurysm development. Further studies on aortic aneurysm pathogenesis and elucidation of the underlying signaling pathways are necessary to identify more novel targets for treating this prevalent and clinical impactful disease.

scholarly journals The Role and Mechanism of SIRT6 in Regulating Phenotype Transformation of Vascular Smooth Muscle Cells in Abdominal Aortic Aneurysm

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Xiaomei Guan ◽  
Hai Xin ◽  
Meiling Xu ◽  
Jianlei Ji ◽  
Jun Li
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Abdominal Aortic ◽  
Phenotype Transformation

Background. Data mining of current gene expression databases has not been previously performed to determine whether sirtuin 6 (SIRT6) expression participates in the pathological process of abdominal aortic aneurysm (AAA). The present study was aimed at investigating the role and mechanism of SIRT6 in regulating phenotype transformation of vascular smooth muscle cells (VSMC) in AAA. Methods. Three gene expression microarray datasets of AAA patients in the Gene Expression Omnibus (GEO) database and one dataset of SIRT6-knockout (KO) mice were selected, and the differentially expressed genes (DEGs) were identified using GEO2R. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of both the AAA-related DEGs and the SIRT6-related DEGs were conducted. Results. GEO2R analysis showed that the expression of SIRT6 was downregulated for three groups and upregulated for one group in the three datasets, and none of them satisfied statistical significance. There were top 5 DEGs (KYNU, NPTX2, SCRG1, GRK5, and RGS5) in both of the human AAA group and SIRT6-KO mouse group. Top 25 ontology of the SIRT6-KO-related DEGs showed that several pathways including tryptophan catabolic process to kynurenine and negative regulation of cell growth were enriched in the tissues of thickness aortic wall biopsies of AAA patients. Conclusions. Although SIRT6 mRNA level itself did not change among AAA patients, SIRT6 may play an important role in regulating several signaling pathways with significant association with AAA, suggesting that SIRT6 mRNA upregulation is a protective factor for VSMC against AAA.

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