Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway
Abstract Objective Previous studies have revealed associations between hyperuricemia and microvascular diseases, but the association between hyperuricemia and abdominal aortic aneurysm (AAA) remains unclear. The aim of this study was to elucidate the pathogenesis and prove the relationship between A...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | BMC Cardiovascular Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12872-022-03012-x |
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| author | Jen-Chun Wang Shih-Hung Tsai Hsiao-Ya Tsai Shing-Jong Lin Po-Hsun Huang |
| author_facet | Jen-Chun Wang Shih-Hung Tsai Hsiao-Ya Tsai Shing-Jong Lin Po-Hsun Huang |
| author_sort | Jen-Chun Wang |
| collection | DOAJ |
| description | Abstract Objective Previous studies have revealed associations between hyperuricemia and microvascular diseases, but the association between hyperuricemia and abdominal aortic aneurysm (AAA) remains unclear. The aim of this study was to elucidate the pathogenesis and prove the relationship between AAA and hyperuricemia. Methods A retrospective study was performed to validate the growth rates of AAA in humans with different serum uric acid levels. A murine model of angiotensin II-induced AAA was used to assess the effects of hyperuricemia on AAA growth in vivo, and human aortic smooth muscle cells (HASMCs) were used to study the pathways involved in these effects in vitro. Results We analyzed data from 107 AAA patients and found that patients with serum uric acid levels above 9 mg/dl had higher AAA growth rates than patients with serum uric acid levels between 4 and 7.9 mg/dl. In vivo, induction of hyperuricemia increased the incidence of AAA formation and the abdominal aortic diameter in mice. The hyperuricemic mice exhibited higher levels of urate transporter 1 (URAT1) expression, phospho-extracellular signal-regulated kinase (p-ERK)1/2 expression, reactive oxygen species (ROS) levels and matrix metalloproteinase (MMP)-9 expression in the abdominal aorta than the control mice. Soluble uric acid increased the expression of URAT1, p-ERK1/2, and MMP-9 and the levels of ROS in HASMCs in vitro. Conclusions We have provided human evidence that hyperuricemia exacerbates AAA formation. In addition, our murine experimental evidence suggests that hyperuricemia exacerbates AAA formation and reveals that the URAT1/ERK1/2/ROS/MMP-9 pathway is among the pathways activated by uric acid in HASMCs. |
| first_indexed | 2024-04-10T17:21:36Z |
| format | Article |
| id | doaj.art-658f356c12e04898a707f77e5185c3fe |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-04-10T17:21:36Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-658f356c12e04898a707f77e5185c3fe2023-02-05T12:04:18ZengBMCBMC Cardiovascular Disorders1471-22612023-01-0123111010.1186/s12872-022-03012-xHyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathwayJen-Chun Wang0Shih-Hung Tsai1Hsiao-Ya Tsai2Shing-Jong Lin3Po-Hsun Huang4Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical CenterDepartment of Emergency Medicine, Tri-Service General Hospital, National Defense Medical CenterDepartment of Emergency Medicine, Tri-Service General Hospital, National Defense Medical CenterInstitute of Clinical Medicine, National Yang-Ming UniversityInstitute of Clinical Medicine, National Yang-Ming UniversityAbstract Objective Previous studies have revealed associations between hyperuricemia and microvascular diseases, but the association between hyperuricemia and abdominal aortic aneurysm (AAA) remains unclear. The aim of this study was to elucidate the pathogenesis and prove the relationship between AAA and hyperuricemia. Methods A retrospective study was performed to validate the growth rates of AAA in humans with different serum uric acid levels. A murine model of angiotensin II-induced AAA was used to assess the effects of hyperuricemia on AAA growth in vivo, and human aortic smooth muscle cells (HASMCs) were used to study the pathways involved in these effects in vitro. Results We analyzed data from 107 AAA patients and found that patients with serum uric acid levels above 9 mg/dl had higher AAA growth rates than patients with serum uric acid levels between 4 and 7.9 mg/dl. In vivo, induction of hyperuricemia increased the incidence of AAA formation and the abdominal aortic diameter in mice. The hyperuricemic mice exhibited higher levels of urate transporter 1 (URAT1) expression, phospho-extracellular signal-regulated kinase (p-ERK)1/2 expression, reactive oxygen species (ROS) levels and matrix metalloproteinase (MMP)-9 expression in the abdominal aorta than the control mice. Soluble uric acid increased the expression of URAT1, p-ERK1/2, and MMP-9 and the levels of ROS in HASMCs in vitro. Conclusions We have provided human evidence that hyperuricemia exacerbates AAA formation. In addition, our murine experimental evidence suggests that hyperuricemia exacerbates AAA formation and reveals that the URAT1/ERK1/2/ROS/MMP-9 pathway is among the pathways activated by uric acid in HASMCs.https://doi.org/10.1186/s12872-022-03012-xHyperuricemiaUric acidUrate transporter 1Matrix metalloproteinaseAbdominal aortic aneurysm |
| spellingShingle | Jen-Chun Wang Shih-Hung Tsai Hsiao-Ya Tsai Shing-Jong Lin Po-Hsun Huang Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway BMC Cardiovascular Disorders Hyperuricemia Uric acid Urate transporter 1 Matrix metalloproteinase Abdominal aortic aneurysm |
| title | Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway |
| title_full | Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway |
| title_fullStr | Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway |
| title_full_unstemmed | Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway |
| title_short | Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway |
| title_sort | hyperuricemia exacerbates abdominal aortic aneurysm formation through the urat1 erk mmp 9 signaling pathway |
| topic | Hyperuricemia Uric acid Urate transporter 1 Matrix metalloproteinase Abdominal aortic aneurysm |
| url | https://doi.org/10.1186/s12872-022-03012-x |
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