Sawicki Grzegorz, Menon Vijayan, Jugdutt Bodh I
Cardiovascular Research Group, Division of Cardiology, University of Alberta, Edmonton, Canada.
J Card Fail. 2004 Oct;10(5):442-9. doi: 10.1016/j.cardfail.2004.01.012.
Angiotensin II (AngII) modulates the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), and AngII type 1 receptor (AT1R) blockers (ARBs) limit left ventricular (LV) dysfunction and remodeling after acute ischemia-reperfusion (IR). Whether ARBs improve TIMP/MMP balance during IR has not been determined.
We measured hemodynamics, LV function, MMP-2 and MMP-9, and TIMP-3 and TIMP-4 in the ischemic zone (IZ) and nonischemic zone (NIZ) after in vivo IR (90 minutes anterior ischemia; 120 minutes reperfusion) in 28 dogs that were randomized to sham, IR controls, and IR plus the ARB valsartan. In controls, IR induced LV dysfunction, infarction, and IZ remodeling; increased MMP-9 and decreased TIMP-3 in the IZ compared with the NIZ (low TIMP-3/MMP-9 ratio); and did not change MMP-2 or TIMP-4. Compared with controls, valsartan (1) limited LV dysfunction, infarct size, and IZ remodeling; (2) increased MMP-2 and MMP-9 and TIMP-3 and -4 in the NIZ; and (3) increased TIMP-3 and the TIMP-3/MMP-9 ratio in the IZ, but did not change MMP-2 and TIMP-4.
Valsartan-induced cardioprotection after IR is associated with enhanced TIMP-3 expression and improved TIMP-3/MMP-9 balance in the in vivo dog model.
血管紧张素II（AngII）调节基质金属蛋白酶（MMPs）与MMPs组织抑制剂（TIMPs）之间的平衡，1型血管紧张素II受体（AT1R）阻滞剂（ARBs）可限制急性缺血再灌注（IR）后左心室（LV）功能障碍和重塑。ARBs是否能改善IR期间的TIMP/MMP平衡尚未确定。
我们在28只犬体内进行IR（90分钟前壁缺血；120分钟再灌注）后，测量了血流动力学、LV功能、MMP-2和MMP-9以及缺血区（IZ）和非缺血区（NIZ）的TIMP-3和TIMP-4。这些犬被随机分为假手术组、IR对照组以及IR加ARB缬沙坦组。在对照组中，IR导致LV功能障碍、梗死和IZ重塑；与NIZ相比，IZ中MMP-9增加而TIMP-3减少（TIMP-3/MMP-9比值低）；且MMP-2或TIMP-4未改变。与对照组相比，缬沙坦（1）限制了LV功能障碍、梗死面积和IZ重塑；（2）增加了NIZ中MMP-2、MMP-9以及TIMP-3和-4；（3）增加了IZ中TIMP-3以及TIMP-3/MMP-9比值，但未改变MMP-2和TIMP-4。
在体内犬模型中，缬沙坦诱导的IR后心脏保护作用与TIMP-3表达增强及TIMP-3/MMP-9平衡改善有关。
