PMID- 30581499 OWN - NLM STAT- MEDLINE DCOM- 20190408 LR - 20220330 IS - 1875-8630 (Electronic) IS - 0278-0240 (Print) IS - 0278-0240 (Linking) VI - 2018 DP - 2018 TI - Differential Gene Expression Profile of Renin-Angiotensin System in the Left Atrium in Mitral Regurgitation Patients. PG - 6924608 LID - 10.1155/2018/6924608 [doi] LID - 6924608 AB - BACKGROUND: Left atrial enlargement is a mortality and heart failure risk factor in primary mitral regurgitation (MR) patients. Pig models of MR have shown differential expression of genes linked to the renin-angiotensin system. Therefore, the aim of this study was to investigate the key genes of the renin-angiotensin that are expressed differentially in the left atrial myocardium in MR patients. METHODS: Quantitative RT-PCR was used to compare gene expression in the renin-angiotensin system in the left atrium in MR patients, aortic valve disease patients, and normal subjects. RESULTS: Plasma angiotensin II concentrations did not significantly differ between MR patients and aortic valve disease patients (P = 0.582). Compared to normal controls, however, MR patients had significantly downregulated expressions of angiotensin-converting enzyme, angiotensin I converting enzyme 2, type 1 angiotensin II receptor, glutamyl aminopeptidase, angiotensinogen, cathepsin A (CTSA), thimet oligopeptidase 1, neurolysin, alanyl aminopeptidase, cathepsin G, leucyl/cystinyl aminopeptidase (LNPEP), neprilysin, and carboxypeptidase A3 in the left atrium. The MR patients also had significantly upregulated expressions of MAS1 oncogene (MAS1) and mineralocorticoid receptor compared to normal controls. Additionally, in comparison with aortic valve disease patients, MR patients had significantly downregulated CTSA and LNPEP expression and significantly upregulated MAS1 expression in the left atrium. CONCLUSIONS: Expressions of genes in the renin-angiotensin system, especially CTSA, LNPEP, and MAS1, in the left atrium in MR patients significantly differed from expressions of these genes in aortic valve disease patients and normal controls. Notably, differences in expression were independent of circulating angiotensin II levels. The results of this study provide a rationale for pharmacological therapies or posttranslational regulation therapies targeting genes expressed differentially in the renin-angiotensin system to remedy structural remodeling associated with atrial enlargement and heart failure progression in patients with MR. FAU - Liu, Wen-Hao AU - Liu WH AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Fang, Yen-Nan AU - Fang YN AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Wu, Chia-Chen AU - Wu CC AD - Division of Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. FAU - Chen, Mien-Cheng AU - Chen MC AUID- ORCID: 0000-0002-3184-4404 AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Chang, Jen-Ping AU - Chang JP AD - Division of Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. FAU - Lin, Yu-Sheng AU - Lin YS AD - Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan. FAU - Pan, Kuo-Li AU - Pan KL AD - Division of Cardiology, Chang Gung Memorial Hospital, Chiayi, Taiwan. FAU - Ho, Wan-Chun AU - Ho WC AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Chang, Tzu-Hao AU - Chang TH AUID- ORCID: 0000-0001-7011-3754 AD - Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan. FAU - Huang, Yao-Kuang AU - Huang YK AD - Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan. FAU - Fang, Chih-Yuan AU - Fang CY AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Chen, Chien-Jen AU - Chen CJ AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Lee, Wei-Chieh AU - Lee WC AUID- ORCID: 0000-0003-0585-6134 AD - Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan. LA - eng PT - Journal Article DEP - 20181118 PL - United States TA - Dis Markers JT - Disease markers JID - 8604127 RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Receptors, G-Protein-Coupled) RN - 11128-99-7 (Angiotensin II) RN - EC 3.4.11.3 (Cystinyl Aminopeptidase) RN - EC 3.4.11.3 (leucyl-cystinyl aminopeptidase) RN - EC 3.4.16.5 (CTSA protein, human) RN - EC 3.4.16.5 (Cathepsin A) SB - IM MH - Aged MH - Angiotensin II/analysis/blood MH - Atrial Function/*genetics MH - Case-Control Studies MH - Cathepsin A/genetics MH - Cystinyl Aminopeptidase/genetics MH - Female MH - *Heart Atria MH - Heart Failure/genetics MH - Heart Valve Diseases/genetics MH - Humans MH - Male MH - Middle Aged MH - Mitral Valve Insufficiency/*genetics MH - Proto-Oncogene Mas MH - Proto-Oncogene Proteins/genetics MH - Receptors, G-Protein-Coupled/genetics MH - Renin-Angiotensin System/*genetics PMC - PMC6276386 EDAT- 2018/12/26 06:00 MHDA- 2019/04/09 06:00 PMCR- 2018/11/18 CRDT- 2018/12/25 06:00 PHST- 2018/07/03 00:00 [received] PHST- 2018/11/01 00:00 [accepted] PHST- 2018/12/25 06:00 [entrez] PHST- 2018/12/26 06:00 [pubmed] PHST- 2019/04/09 06:00 [medline] PHST- 2018/11/18 00:00 [pmc-release] AID - 10.1155/2018/6924608 [doi] PST - epublish SO - Dis Markers. 2018 Nov 18;2018:6924608. doi: 10.1155/2018/6924608. eCollection 2018.