Key result
Higher Agt expression in mice alters hypertension genes, including a ~3-fold increase in aldosterone synthase.
Why the study?
The human angiotensinogen M235T polymorphism is linked to differential AGT expression and hypertension, but the homeostatic responses resulting from this polymorphism are not known.
Does genetically determined angiotensinogen gene expression alter the expression of hypertension-related genes and blood pressure in mice?
Does genetically determined angiotensinogen gene expression alter the expression of hypertension-related genes and blood pressure in mice?
Moderate alterations in angiotensinogen gene expression induce significant, sex-specific changes in the expression of hypertension-related genes and blood pressure in mice.
Supports angiotensinogen modulation in mouse hypertension models; hypothesis-generating with no implications for human practice.
The angiotensinogen M235T polymorphism in humans is linked to differential expression of the human angiotensinogen gene (AGT) gene and hypertension, but the homeostatic responses resulting from this polymorphism are not known. We therefore investigated how mice respond to five genetically determined levels of mouse angiotensinogen gene (Agt) expression covering the range associated with the M235T variants. By using high-throughput molecular phenotyping, tissue RNAs were assayed for expression of 10 genes important in hypertension. Significant positive and negative responses occurred in both sexes as Agt expression increased twofold, including a three-fold increase in aldosterone synthase expression in adrenal gland, and a two-fold decrease in renin expression in kidney. In males, cardiac expression of the precursor of atrial natriuretic peptide B and of adrenomedullin also increased approximately twofold. The relative expression of all genes studied except Agt differed significantly in the two sexes, and several unexpected relationships were encountered. A highly significant correlation between renal expression of the angiotensin type 1a receptor and kallikrein, independent of Agt genotype, is present in females (P < 0.0001) but not males (P = 0.4). The correlation between blood pressure (BP) and liver Agt expression within the five Agt genotypes is significant in females (P = 0.0005) but not in males (P = 0.2), whereas correlation of BP with differences between the genotypes is less in females (P = 0.06) than in males (P = 0.001). The marked gender differences in gene expression in wild-type mice and the changes induced by moderate alterations in Agt expression and BP emphasize the need to look for similar differences in humans.
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John et al. (2020) studied Hypertension. Genetically determined levels of mouse angiotensinogen gene (Agt) expression vs. Different Agt genotypes / wild-type mice was evaluated on Tissue RNA expression of 10 genes important in hypertension and blood pressure. In mice, a twofold increase in Agt expression led to significant changes in hypertension-related gene expression, including a threefold increase in adrenal aldosterone synthase and a twofold decrease in renal renin.
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