Reversal of endocardial endothelial dysfunction by folic acid in homocysteinemic hypertensive rats
Reversal of endocardial endothelial dysfunction by folic acid in homocysteinemic hypertensive rats
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DOI：
10.1016/s0895-7061(01)02286-5
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发表时间：
2002-02-01
影响因子：
3.2
通讯作者：
Tyagi, SC
中科院分区：
文献类型：
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作者：
Miller, A;Mujumdar, V;Tyagi, SC
同型半胱氨酸（Hcy）的L-和d -异构体在血管与心内膜内皮（EE）重塑和功能中的作用尚不清楚。假设Hcy通过激活基质金属蛋白酶（MMP）和诱导左心室肥厚（LVH）降低同型半胱氨酸高血压大鼠（HHR） EE细胞密度。Hcy的L-和d -异构体在血管和心肌中有不同的作用。我们使用：1)内源性总同囊(e)线（tHcy）水平中等高（18 μ mol/L）的自发性高血压大鼠（SHR）；2)对照年龄和性别匹配的正常Wistar大鼠（NWR），其中tHcy水平正常（4 μ mol/L）；为了造成高同囊血症（e)，在3)SHR （SHR- h）和4）NWR （NWR- h）大鼠中给药32 mg/天Hcy，持续12周，叶酸（SHR- f）使SHR中内源性tHcy水平从18 μ mol/L降低到12 μ mol/L。采用高效液相色谱法和分光光度法测定血浆tHcy水平。酶谱法测定的MMP活性随着慢性Hcy的使用而增加，而叶酸治疗则降低了MMP活性。逆转录-聚合酶链反应测定的胶原蛋白和转化生长因子- β (1) （tgf - β(1)）被Hcy增加。叶酸治疗降低胶原蛋白表达并增加tgf - β(1)。在麻醉大鼠左心室通过导管测量左室功能。服用叶酸后SHR中tHcy水平部分下降，动脉压无变化，提示叶酸降低了Hcy的L-或d -异构体中的一种，这不是动脉压升高的原因，但可能是心肌功能障碍的原因。慢性给药可降低NWR和SHR的EE功能。叶酸治疗SHR可改善LVH和EE功能。叶酸通过降低Hcy的一种D-或l -异构体和降低HHR的MMP活性来改善心脏重塑和EE功能。这些结果可能提示L-和d -异构体在血管和心脏重构中的不同作用。Am J Hypertens 2002；[15]中华医学杂志，2002。
The role of L- and D-isomers of homocysteine (Hcy) in vascular versus endocardial endothelial (EE) remodeling and function is not well understood. The hypothesis is that Hcy decreases EE cell density by activating matrix metalloproteinase (MMP) and by inducing left ventricular hypertrophy (LVH) in homocysteinemic hypertensive rats (HHR). And L- and D-isomers of Hcy have differential effects in vessel and myocardium. We used: 1) spontaneously hypertensive rats (SHR) in which endogenous total homocyst(e)ine (tHcy) levels are moderately high (18 mumol/L); 2) control age- and sex-matched normotensive Wistar rats (NWR) in which tHcy levels are normal (4 mumol/L); to create hyperhomocyst(e)inemia, 32 mg/day Hcy was administered for 12 weeks in 3) SHR (SHR-H), and in 4) NWR (NWR-H) rats, 5) endogenous tHcy levels were reduced (from 18 to 12 mumol/L) in SHR by folic acid administration (SHR-F). Plasma tHcy levels were measured by HPLC and spectrophometric methods. The MMP activity, measured by zymography, is increased by chronic Hcy administration, and folic acid treatment decreases MMP activity. The collagen and transforming growth factor-beta(1) (TGF-beta(1)), measured by reverse transcriptase-polymerase chain reaction, are increased by Hcy. Folic acid treatment decreases collagen expression and increases TGF-beta(1). In vivo LV function was measured in anesthetized rats by a catheter in the left ventricle. The partial decrease in tHcy levels and no change in arterial pressure in SHR after folic acid administration, suggested that folic acid decreases one of the L- or D-isomer of Hcy, which is not responsible for an increase in arterial pressure, but may be responsible for myocardial dysfunction. The chronic Hcy administration decreases EE function in NWR and SHR. The treatment of folic acid in SHR improves LVH and EE function. Folic acid improves cardiac remodeling and EE function by decreasing one of the D- or L-isomer of Hcy and by decreasing MMP activity in HHR. These results may suggest a differential role Of L- and D-isomers in vascular versus cardiac remodeling. Am J Hypertens 2002;15:157-163 (C) 2002 American Journal of Hypertension, Ltd.