López Begoña, González Arantxa, Querejeta Ramón, Larman Mariano, Díez Javier
Division of Cardiovascular Sciences, Centre for Applied Medical Research, School of Medicine, University of Navarra, Pamplona, Spain.
J Am Coll Cardiol. 2006 Jul 4;48(1):89-96. doi: 10.1016/j.jacc.2006.01.077. Epub 2006 Jun 12.
We sought to assess the distribution of collagen deposits and collagen degradation in hypertensive patients with either systolic heart failure (SHF) or diastolic heart failure (DHF).
Increased collagen synthesis and deposition have been described in the myocardium of heart failure (HF) hypertensive patients.
We studied 39 HF hypertensive patients subdivided into two groups: 16 with SHF and 23 with DHF. Endomyocardial biopsies were performed to quantify mysial (i.e., perimysial plus endomysial) and perivascular and scar-related collagen volume fraction (CVF). Matrix metalloproteinase (MMP)-1 and its tissue inhibitor matrix metalloproteinase (TIMP)-1 were analyzed in cardiac samples by Western blot and immunohistochemistry, and in blood samples by enzyme-linked immunosorbent assay.
Mysial CVF was lower in SHF hypertensive patients than in normotensive (p < 0.05) and DHF hypertensive patients (p < 0.01). Perivascular and scar-related CVF was higher (p < 0.05) in the two groups of hypertensive patients than in normotensive subjects, and in SHF hypertensive compared with DHF hypertensive patients. The MMP-1:TIMP-1 ratio was increased (p < 0.05) in tissue and serum samples from the SHF hypertensive group compared with the other two groups of subjects. The MMP-1 expression was increased (p < 0.01) in the interstitium and cardiomyocytes of SHF hypertensive patients compared with DHF hypertensive and normotensive subjects. The serum MMP-1:TIMP-1 ratio was inversely correlated with ejection fraction (r = -0.510, p < 0.001) and directly correlated with left ventricular end-diastolic diameter (r = 0.549, p < 0.001) in all subjects.
These findings show that the pattern of collagen deposits and the balance of the MMP-1/TIMP-1 system are different in the myocardium of SHF and DHF hypertensive patients. It is proposed that excessive degradation of mysial collagen may be related to the compromise of systolic function in HF hypertensive patients.
我们试图评估收缩性心力衰竭(SHF)或舒张性心力衰竭(DHF)的高血压患者中胶原沉积和胶原降解的分布情况。
已有研究描述心力衰竭(HF)高血压患者心肌中胶原合成和沉积增加。
我们研究了39例HF高血压患者,分为两组:16例SHF患者和23例DHF患者。进行心内膜活检以量化肌束内(即肌束膜加肌内膜)、血管周围和瘢痕相关的胶原容积分数(CVF)。通过蛋白质免疫印迹法和免疫组织化学法分析心脏样本中的基质金属蛋白酶(MMP)-1及其组织抑制剂基质金属蛋白酶(TIMP)-1,并通过酶联免疫吸附测定法分析血液样本中的MMP-1和TIMP-1。
SHF高血压患者的肌束内CVF低于正常血压患者(p < 0.05)和DHF高血压患者(p < 0.01)。两组高血压患者的血管周围和瘢痕相关CVF均高于正常血压受试者,且SHF高血压患者高于DHF高血压患者(p < 0.05)。与其他两组受试者相比,SHF高血压组的组织和血清样本中MMP-1:TIMP-1比值升高(p < 0.05)。与DHF高血压患者和正常血压受试者相比,SHF高血压患者的间质和心肌细胞中MMP-1表达增加(p < 0.01)。在所有受试者中,血清MMP-1:TIMP-1比值与射血分数呈负相关(r = -0.510,p < 0.001),与左心室舒张末期直径呈正相关(r = 0.549,p < 0.001)。
这些发现表明,SHF和DHF高血压患者心肌中的胶原沉积模式以及MMP-1/TIMP-1系统的平衡不同。有人提出,肌束内胶原的过度降解可能与HF高血压患者的收缩功能受损有关。