Effects of the angiotensin receptor blocker candesartan on arterial stiffness and markers of extracellular matrix metabolism in patients with essential hypertension
Effects of the angiotensin receptor blocker candesartan on arterial stiffness and markers of extracellular matrix metabolism in patients with essential hypertension
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DOI：
10.1080/10641960600798721
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发表时间：
2006-07-01
影响因子：
12.3
通讯作者：
Saruta, Takao
中科院分区：
文献类型：
--
作者：
Sasamura, Hiroyuki;Kitamura, Yudai;Saruta, Takao
实验室研究表明，血管紧张素受体阻滞剂(ARB)可以影响细胞外基质(ECM)的代谢，从而对血管重塑有有益的影响。本研究的目的是探讨ARB坎地沙坦酯对高血压患者血清ECM合成和降解标志物的影响及其与动脉僵硬改变的关系。研究对象为23例高血压病患者。在坎地沙坦治疗前和治疗1年后，检测与细胞外基质合成和降解相关的标志物(前胶原I型前肽[PIP]、III型前胶原前肽[PIIIP]、基质金属蛋白酶-3[MMP3、基质分解素-1]、基质金属蛋白酶组织抑制因子[TIMP-1]和透明质酸[HA])。分别于降压后2个月和治疗1年后测量脉搏波速度[PWV]和踝臂压指数[ABI]。ARB治疗一年后，PWV值较治疗前显著降低，而ABI值无明显变化。ARB治疗还与血清PIIIP值显著降低和血清基质分解素-1升高有关，而PIP、TIMP-1和HA的变化没有统计学意义。校正血压和心率后PWV的变化与基质分解素-1水平的变化之间存在显著的相关性(p=0.02)。这些结果表明，仅用ARB治疗一年，ECM代谢的标志物和PWV就会发生显着变化。这些对细胞外基质代谢的影响可能对减轻高血压病患者的血管病变有有益的作用。
Laboratory studies have shown that angiotensin receptor blockers (ARBs) can affect extracellular matrix (ECM) metabolism and thereby have a beneficial effect on vascular remodeling. The aim of this study was to examine the clinical effects of the ARB candesartan cilexetil on serum markers of synthesis and degradation of ECM, as well as their relation to changes in arterial stiffness in hypertensive patients. Twenty-three patients with essential hypertension were recruited for this study. Markers related to ECM synthesis and degradation (procollagen type 1 propeptide [PIP], procollagen type III propeptide [PIIIP], matrix metalloproteinase-3 [MMP-3, stromelysin-1], tissue inhibitor of matrix metalloproteinases [TIMP-1], and hyaluronic acid [HA]) were examined both before and after one year of treatment with candesartan. Pulse-wave velocity [PWV] and ankle-brachial pressure index [ABI] were measured two months (i.e., after achieving blood pressure reduction) and one year after the initiation of therapy. PWV values after one year of treatment with ARB were significantly decreased compared to previous values, whereas ABI values were unchanged. Treatment with ARB was also associated with a significant decrease in serum PIIIP values and an increase in serum stromelysin-1, whereas changes in PIP, TIMP-1, and HA did not achieve statistical significance. A significant relationship was found between the changes in PWV and the changes in stromelysin-1 levels after correction for blood pressure and heart rate ( p =0.02). These results suggest that the treatment for just one year with ARB results in significant changes in markers of ECM metabolism as well as PWV. These effects on ECM metabolism could have a beneficial effect in decreasing vascular pathology in patients with essential hypertension.