Abstract
Parathyroid hormone (PTH) treatment was previously shown to improve cardiac function after myocardial infarction by enhancing neovascularization and cell survival. In this study, pressure overload-induced left ventricular hypertrophy (LVH) was induced in mice by transverse aortic banding (TAB) for 2 weeks. We subsequently evaluated the effects of a 2-week treatment with PTH or saline on compensated LVH. After another 4 weeks, the hearts of the mice were analyzed by echocardiography, histology, and molecular biology. Echocardiography showed that hearts of the PTH-treated mice have more severe failing phenotypes than the saline-treated mice following TAB with a greater reduction in fractional shortening and left ventricular posterior wall thickness and with a greater increase in left ventricular internal dimension. Increases in the heart weight to body weight ratio and lung weight to body weight ratio following TAB were significantly exacerbated in PTH-treated mice compared to saline-treated mice. Molecular markers for heart failure, fibrosis, and angiogenesis were also altered in accordance with more severe heart failure in the PTH-treated mice compared to the saline-treated mice following TAB. In addition, the PTH-treated hearts were manifested with increased fibrosis accompanied by an enhanced SMAD2 phosphorylation. These data suggest that the PTH treatment may accelerate the process of decompensation of LV, leading to heart failure.
Highlights
Parathyroid hormone (PTH) plays a role in calcium homeostasis, and PTH expression is regulated by the calcium concentration
The TABoperated mice (n = 36) were re-examined by echocardiography, and the mice (n = 18) with compensated left ventricular hypertrophy (LVH) (> 30% increase in interventricular septum thickness at diastole, IVSTd, and > 40% of fractional shortening, FS) were selected and randomly divided into transverse aortic banding (TAB)/Saline (n = 9) and TAB/PTH (n = 9) groups
Echocardiographic, histological, and molecular analyses were conducted. We chose this time point for final phenotypic and molecular analyses because a mice strain C57BL/6 used in this study usually showed typical heart failure phenotypes at eight weeks postbanding
Summary
Parathyroid hormone (PTH) plays a role in calcium homeostasis, and PTH expression is regulated by the calcium concentration. A low calcium level in the plasma triggers the secretion of PTH from the parathyroid gland. The secreted PTH raises the calcium level in plasma by promoting the release of calcium from bone, reducing the calcium excretion by the kidneys, and increasing the calcium absorption by the small intestine. The increased calcium level inhibits PTH secretion from the parathyroid gland (Pocotte et al, 1991). In addition to traditionally known target organs such as bone, kidney, and small intestine, the ventricular cardiomyocytes were reported to be targets of PTH (Schluter and Piper, 1992). No significant correlation between the left ventricular mass and PTH level was found in the general population (Saleh et al, 2003). The role of PTH in the development of left ventricular hypertrophy (LVH) has remained obscure
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