Key result
Stenotic aortic valves linked to higher ACE and chymase expression and ~6-fold more mast cells.
Why the study?
The detailed molecular mechanisms involving angiotensin II-producing enzyme systems in the pathogenesis of aortic stenosis remain obscure.
Observational (n=97)
p-value: p=<0.001
Laboratory tissue analysis reveals upregulation of local angiotensin II-producing pathways in stenotic aortic valves, indicating a direct role in progressive valvular remodeling.
OBJECTIVES: The purpose of this study was to investigate the expression of angiotensin II (Ang II)-producing enzyme systems in normal and stenotic aortic valves. BACKGROUND: Chronic inflammation and fibrosis are involved in the pathogenesis of aortic stenosis (AS), but the detailed molecular mechanisms of this atherosclerosis-like process remain obscure. Angiotensin II, a powerful mediator of inflammation and fibrosis, may participate in AS progression. METHODS: Stenotic aortic valves (n = 86) were obtained from patients undergoing valve replacement surgery, and control valves (n = 11) were obtained from patients undergoing cardiac transplantation. Angiotensin-converting enzyme (ACE) and mast cell (MC)-derived chymase were quantified by reverse-transcription polymerase chain reaction, autoradiography, and immunostaining. The MCs, macrophages, and T lymphocytes were detected by immunohistochemistry, and angiotensin II type 1 receptor (AT-1R) by autoradiography. RESULTS: Compared with control valves, stenotic aortic valves showed a significant increase in both messenger ribonucleic acid (mRNA) (p = 0.001) and protein (p < 0.001) expression of ACE, which colocalized with macrophages. Similarly, the expression of AT-1R protein and chymase mRNA and protein was upregulated (p < 0.001), and the number of MCs was six-fold higher in stenotic than in normal valves. The MCs were associated with the calcified areas, and-in contrast to control valves-showed an increased degree of degranulation, a prerequisite for chymase secretion and action. CONCLUSIONS: Angiotensin-converting enzyme and chymase, two Ang II-forming enzymes, are locally expressed in aortic valves, and owing to infiltration of macrophages and MCs, are further upregulated in stenotic valves. These novel findings, implicating chronic inflammation and an increased expression of local Ang II-forming systems, suggest that therapeutic interventions aiming at inhibiting these processes may slow AS progression.
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Helske et al. (2004) conducted an observational in Aortic stenosis (n=97). Stenotic aortic valves vs. Normal control valves was evaluated on Expression of angiotensin-converting enzyme (ACE) and chymase (p=<0.001). Stenotic aortic valves had significantly higher expression of angiotensin-converting enzyme and chymase, and a six-fold higher number of mast cells compared to control valves.
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