Dataset Information

Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms.

ABSTRACT: Aneurysms and dissections affecting thoracic aorta are associated with smooth muscle cell (SMC) dysfunction. NO/cGMP signaling pathway in smooth muscle cells has been shown to be affected in sporadic thoracic aortic aneurysms. We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. We found that aortic tissue obtained from Marfan, tricuspid and bicuspid thoracic aneurysms expressed lower levels of PDE5 mRNA compared to control aortas. In particular, we found that affected aortas showed lower levels of all the PDE5A isoforms, compared to control aortas. Transfection of vascular SMCs (VSMCs) with NOTCH3 activated domain (NICD3) induced the expression of PDE5A1 and A3 protein isoforms, but not that of the corresponding mRNAs. VSMC stimulation with GSNO, a nitric oxide analogue or with 8-br-cGMP, but not with 8-br-cAMP, up-regulated PDE5 and NOTCH-3 protein levels, indicating a negative feedback loop to protect the arterial wall from excessive relaxation. Finally, we found that PDE5 is expressed early during human aorta development, suggesting that if loss of function mutations of PDE5 occur, they might potentially affect aortic wall development.

SUBMITTER: Cesarini V

PROVIDER: S-EPMC6704119 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms.

Cesarini Valeriana V Pisano Calogera C Rossi Gabriele G Balistreri Carmela Rita CR Botti Flavia F Antonelli Giorgio G Ruvolo Giovanni G Jannini Emmanuele A EA Dolci Susanna S

Scientific reports 20190821 1

Aneurysms and dissections affecting thoracic aorta are associated with smooth muscle cell (SMC) dysfunction. NO/cGMP signaling pathway in smooth muscle cells has been shown to be affected in sporadic thoracic aortic aneurysms. We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. We found that aortic tissue obtained from Marfan, tricuspid and bicuspid thoracic aneurysms expressed lower level ...[more]

PMID: 31434939

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Project description:Background Patients undergoing surgery for thoracic aortic aneurysms receive statin therapy out of proportion to cardiovascular comorbidity. We sought to determine the prevalence of statin use among patients presenting for thoracic aortic aneurysm surgery and investigate its effect on outcomes.Methods From January 1, 2005 to January 1, 2011, 1,839 consecutive patients underwent aortic replacement for degenerative thoracic aortic aneurysm at Cleveland Clinic. Of these, 771 (42%) were on statins preoperatively. Statin users (vs. nonstatin users) were older (65 ± 11 vs. 56 ± 16 years) and had more hypertension (78 vs. 59%). Propensity matching based on 56 preoperative variables other than lipid levels was used to compare outcomes among 570 matched patient pairs (74% of possible pairs).Results Propensity-matched statin and nonstatin users were aged 64 ± 11 years, 394 (69%) versus 387 (68%) were male, and 437 (77%) versus 442 (78%) had ascending aortic aneurysms, respectively. Overall, 25% of patients were followed for more than 8.2 years and 10% for more than 10 years. Perioperative outcomes were similar, including hospital mortality (11 [1.9%] vs. 5 [0.88%]) and stroke (22 [3.9%] vs. 13 [2.3%]), but 16 statin users (2.8%) versus 5 nonstatin users (0.88%) required temporary dialysis after surgery (p = 0.02). At 6 years, 3.7% of statin users versus 5.1% of nonstatin users (p[log-rank] = 0.5) underwent further aortic surgery, and at 10 years, mortality was 25% in both groups (p > 0.5).Conclusion Patients presenting for thoracic aortic aneurysm surgery frequently receive unnecessary statins. Additionally, statin use was associated with more postoperative renal failure, but not less intermediate-term risk for aortic reintervention or all-cause mortality after surgery. Therefore, presence of a thoracic aortic aneurysm should not be considered an indication for statin therapy in the absence of well-established indications.

Dataset Information

Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms.

Publications

Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms.

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