Associations Between miR-145, TGF-β Signaling, and Aortic Wall Remodeling in Abdominal Aortic Aneurysm.
4 affiliations
- 1Özel Pendik Bölge Hastanesi, Istanbul 34890, Turkey.
- 2Memorial Göztepe Hospital, Istanbul 34634, Turkey.
- 3Department of Medical Biology and Genetics, Istanbul Okan University, Istanbul 34959, Turkey.
- 4Department of Medical Genetics, Tehran University of Medical Sciences, Tehran 14176, Iran.
Abstract
Background/purpose: Abdominal aortic aneurysm (AAA) is characterized by pathological remodeling of the aortic wall, involving vascular smooth muscle cell (VSMC) dysfunction, extracellular matrix degradation, and alterations in signaling pathways. MicroRNA-145 (miR-145) is involved in the regulation of VSMC phenotype, whereas transforming growth factor-beta (TGF-β) signaling has context-dependent effects on vascular remodeling. This study used a dataset to explore potential associations between miR-145 expression, TGF-β/SMAD signaling, VSMC phenotypic characteristics, and structural features of the aortic wall. Methods: Aortic tissue samples were obtained from 324 patients with AAA during aneurysm-related surgical treatment. Control tissues were collected from macroscopically healthy aortic segments of 324 subjects undergoing elective cardiothoracic or vascular surgery. Tissue samples were analyzed for miR-145 expression, TGF-β signaling, vascular smooth muscle cell markers, and histopathological characteristics of aortic wall remodeling. Results: miR-145 was significantly downregulated in AAA tissue compared to control. RT-qPCR, Western blotting, and immunohistochemistry revealed increased TGF-β1/TGFBR signaling, SMAD2/3 activation, and KLF4 expression, accompanied by reduced expression of the VSMC contractile genes ACTA2, TAGLN, and MYH11, in AAA tissue. The lower expression level of miR-145 correlated significantly with TGF-β/SMAD pathway activation, VSMC phenotypic switching, more pronounced medial degeneration and elastic-fiber fragmentation, and increased aortic diameter (p < 0.001). Conclusions: Lower miR-145 expression was associated with TGF-β/SMAD pathway-related activity, altered VSMC phenotype, and structural remodeling of the aortic wall in AAA tissue. These findings identify a potential association between miR-145 dysregulation and TGF-β-associated vascular remodeling; however, they do not establish a direct functional signaling axis or causal relationship. Further mechanistic studies are required to clarify the underlying molecular interactions.
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BibTeX
@article{kaya2026associations,
title = {{Associations Between miR-145, TGF-β Signaling, and Aortic Wall Remodeling in Abdominal Aortic Aneurysm.}},
author = {Erhan Kaya and Hidayet Demir and Mehrdad Sheikhvatan},
journal = {Genes},
year = {2026},
month = sep,
doi = {10.3390/genes17101183},
url = {https://europepmc.org/article/MED/42938299},
note = {CC BY},
}
RIS
TY - JOUR
TI - Associations Between miR-145, TGF-β Signaling, and Aortic Wall Remodeling in Abdominal Aortic Aneurysm.
AU - Erhan Kaya
AU - Hidayet Demir
AU - Mehrdad Sheikhvatan
PY - 2026
DA - 2026/09/24
JO - Genes
DO - 10.3390/genes17101183
UR - https://europepmc.org/article/MED/42938299
AB - Background/purpose: Abdominal aortic aneurysm (AAA) is characterized by pathological remodeling of the aortic wall, involving vascular smooth muscle cell (VSMC) dysfunction, extracellular matrix degradation, and alterations in signaling pathways. MicroRNA-145 (miR-145) is involved in the regulation of VSMC phenotype, whereas transforming growth factor-beta (TGF-β) signaling has context-dependent effects on vascular remodeling. This study used a dataset to explore potential associations between miR-145 expression, TGF-β/SMAD signaling, VSMC phenotypic characteristics, and structural features of the aortic wall. Methods: Aortic tissue samples were obtained from 324 patients with AAA during aneurysm-related surgical treatment. Control tissues were collected from macroscopically healthy aortic segments of 324 subjects undergoing elective cardiothoracic or vascular surgery. Tissue samples were analyzed for miR-145 expression, TGF-β signaling, vascular smooth muscle cell markers, and histopathological characteristics of aortic wall remodeling. Results: miR-145 was significantly downregulated in AAA tissue compared to control. RT-qPCR, Western blotting, and immunohistochemistry revealed increased TGF-β1/TGFBR signaling, SMAD2/3 activation, and KLF4 expression, accompanied by reduced expression of the VSMC contractile genes ACTA2, TAGLN, and MYH11, in AAA tissue. The lower expression level of miR-145 correlated significantly with TGF-β/SMAD pathway activation, VSMC phenotypic switching, more pronounced medial degeneration and elastic-fiber fragmentation, and increased aortic diameter (p < 0.001). Conclusions: Lower miR-145 expression was associated with TGF-β/SMAD pathway-related activity, altered VSMC phenotype, and structural remodeling of the aortic wall in AAA tissue. These findings identify a potential association between miR-145 dysregulation and TGF-β-associated vascular remodeling; however, they do not establish a direct functional signaling axis or causal relationship. Further mechanistic studies are required to clarify the underlying molecular interactions.
SN - 2073-4425
ER -