Remodeling of cardiac structure in patients with primary aldosteronism.
Date Issued
2011
Date
2011
Author(s)
Lin, Yen-Hung
Abstract
Primary aldosteronism (PA) is a curable and common hypertensive disease, and is characterized by an inappropriate production of aldosterone. PA, the prevalence of which is around 5-10% of patients with hypertension, consists of two subtypes: aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA).
Patients with PA have been shown to have a higher prevalence of cardiovascular events and atrial fibrillation than patients with essential hypertension (EH), which are independent of blood pressure effects. In addition, patients with PA have a more prominent left ventricular (LV) mass, and a higher degree of LV diastolic function impairment and myocardial fibrosis than those with EH. In recent studies, macrophage-mediated low grade inflammation has been shown to play an important role in aldosterone-inducing cardiac fibrosis. However, the mediators of this process are still unclear.
In order to investigate the change of cardiac structure and texture in PA patients and their relation to macrophage, we designed a series of studies. In the part, we found that serum potassium level was negatively associated with LV mass index (LVMI) in PA patients. Compared with patients with EH, PA patients had a greater impairment of cardiac diastolic function, which was independent of serum potassium level. In the second part, we found that LV hypertrophy in PA patients could be significantly reversed by adrenalectomy. Pre-operative LVMI and change of systolic blood pressure were associated with the degree of LVMI decrease. In the third and fourth part, we found that adrenalectomy reversed not only LV geometry but also altered myocardial texture in patients with unilateral hyperaldosteronism. This suggests that increases in collagen content in the myocardium of patients with unilateral hyperaldosteronism might be reversed by adrenalectomy.
In the fifth part, we investigated whether aldosterone induced macrophage to secret galectin-3 and its mechanisms. We found that aldosterone induced the THP-1 cell to secret galectin-3 via mineralocorticoid receptors. The induced secretion occurred through the PI3K/Akt pathway, and NF-kB was an important transcriptional factor in this pathway. In the sixth part, we investigated whether aldosterone induced macrophage to secret IL-6 and its mechanisms. We found that aldosterone induced the THP-1 cell to secret IL-6 via mineralocorticoid receptors. The induced secretion was achieved through the PI3K/Akt and p38 pathway, and NF-kB and NF-IL-6 were important transcriptional factors in this pathway. In the seventh part, we found that patients with APA had higher plasma IL-6 levels than EH patients’ and the increased plasma IL-6 concentration decreased significantly one year after adrenalectomy in the APA patients. However, plasma galectin-3 levels were comparable in both groups, and there was also no change one year after adrenalectomy in the APA patients.
As hypertension is an important risk factor of cardiovascular disease, and as PA is a curable and common hypertensive disease, the issues of PA are becoming increasingly important. It is hoped that these studies will promote a greater understanding of PA and its effect on the cardiovascular system.
Key words: primary aldosteronism; aldosterone; left ventricular hypertrophy; cardiac fibrosis; IL-6; galectin-3
Subjects
primary aldosteronism
aldosterone
left ventricular hypertrophy
cardiac fibrosis
SDGs
Type
thesis
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