Hyperphosphatemia aggravates cardiac fibrosis and microvascular disease in experimental uremia
Hyperphosphatemia aggravates cardiac fibrosis and microvascular disease in experimental uremia
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DOI：
10.1046/j.1523-1755.2003.00864.x
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发表时间：
2003-04-01
影响因子：
19.6
通讯作者：
Ritz, E
中科院分区：
文献类型：
--
作者：
Amann, K;Törnig, J;Ritz, E
背景高磷血症是已知的心血管死亡的预测因子，特别是血液透析患者的心源性死亡。所涉及的病理机制尚未完全阐明。虽然一些观察结果表明，高磷血症和正钙平衡的冠状动脉导管动脉粥样硬化和钙化的重要作用，独立的影响冠状动脉后微血管和心脏纤维化尚未被排除。对雄性Sprague-Dawley大鼠进行假手术（N = 14）或肾次全切除（SNX，N = 17），随后在配对喂养条件下给予低磷（0.08% w/w）和高磷（1.2% w/w）饮食。8周后，测量血清化学和抑制性甲状旁腺激素（iPTH），并使用灌注固定收获心脏。采用体视学技术定量测量小动脉厚度和血管体积密度。在中度肾功能衰竭的SNX动物中，低磷饮食的血清磷浓度（1.7 +/- 0.37 mmol/L）高于假手术对照组，SNX +高磷饮食（2.33 +/- 0.23 mmol/L）显著高于SNX +低磷饮食（1.95 +/- 0.32 mmol/L; P < 0.05）。在假手术对照组中，膳食磷含量对心脏形态指标没有影响。相比之下，在SNX +高磷饮食中，间质性心脏纤维化指数（3.22 +/- 0.44%）显著高于SNX +低磷（2.75 +/- 0.46%）或假手术对照（分别为高磷2.5 +/- 0.05%和低磷2.4 +/- 0.89）。在SNX +高磷（14.0 +/- 9.0 μ m）中，但在SNX +低磷（9.2 +/- 4.5 μ m）中，动脉壁厚度显著高于假手术对照组（分别为高磷10.2 +/- 5.1 μ m和低磷9.8 +/- 5.0 μ m）。结论：本实验结果与文献报道一致。高磷饮食和高磷血症对心脏纤维化和动脉壁增厚有显著影响。这种心脏结构的异常可能与高磷血症尿毒症患者的心脏风险增加有关。
Background. Hyperphosphatemia is a known predictor of cardiovascular death and specifically of cardiac death in hemodialysis patients. The pathomechanisms involved have not been completely clarified. While a number of observations suggest an important role of hyperphosphatemia and positive calcium balance on atherosclerosis and calcification of the coronary conduit arteries, independent effects on postcoronary microvessels and on cardiac fibrosis have not been excluded.Methods. Male Sprague-Dawley rats were sham operated (N = 14) or subtotally nephrectomized (SNX, N = 17) and subsequently placed on low phosphorus (0.08% w/w) and high phosphorus (1.2% w/w) diet under pair-feeding conditions. After 8 weeks, serum chemistry and inhibitory parathyroid hormone (iPTH) were measured, and the hearts were harvested using perfusion fixation. Arteriolar thickness and volume density of the interstitium (excluding vessels) were quantitated using stereologic techniques.Results. In SNX animals with moderate renal failure serum phosphorus concentrations were higher than in sham-operated controls on low phosphorus diet (1.7 +/- 0.37 mmol/L) and were significantly higher in SNX + high phosphorus diet (2.33 +/- 0.23 mmol/L) compared to SNX + low phosphorus diet (1.95 +/- 0.32 mmol/L; P < 0.05). In sham-operated controls, dietary phosphorus content had no effect on cardiac morphologic indices. In contrast, in SNX + high phosphorus diet the index of interstitial cardiac fibrosis was significantly higher (3.22 +/- 0.44%) than in SNX + low phosphorus (2.75 +/- 0.46%) or in sham-operated controls (2.5 +/- 0.05% on high phosphorus and 2.4 +/- 0.89 on low phosphorus, respectively). In SNX + high phosphorus (14.0 +/- 9.0 mu m), but not in SNX + low phosphorus (9.2 +/- 4.5 mu m), arterial wall thickness was significantly higher compared to sham-operated controls (10.2 +/- 5.1 on high phosphorus and 9.8 +/- 5.0 mu m on low phosphorus, respectively). The data were confirmed in an independent repeat experiment.Conclusion. High dietary phosphorus and hyperphosphatemia have significant effects on cardiac fibrosis and arterial wall thickening. Such abnormalities of cardiac architecture may be relevant for the increased cardiac risk in hyperphosphatemic uremic patients.