Key result
Left atrial gene expression of CTSA, LNPEP, and MAS1 significantly differed in mitral regurgitation patients versus controls, independent of plasma angiotensin II levels (P=0.582 vs aortic disease).
Why the study?
Left atrial enlargement is a mortality and heart failure risk factor in primary MR, and pig MR models show differential renin-angiotensin system gene expression.
Observational
Patients with primary mitral regurgitation exhibit a distinct gene expression profile of the renin-angiotensin system in the left atrium compared to those with aortic valve disease and normal controls, providing a potential rationale for targeted pharmacological therapies.
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.
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Liu et al. (2018) conducted an observational in Primary mitral regurgitation. Mitral regurgitation vs. Aortic valve disease patients and normal subjects was evaluated on Gene expression in the renin-angiotensin system in the left atrium. Left atrial gene expression of CTSA, LNPEP, and MAS1 significantly differed in mitral regurgitation patients versus controls, independent of plasma angiotensin II levels (P=0.582 vs aortic disease).
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