López B, Querejeta R, Varo N, González A, Larman M, Martínez Ubago J L, Díez J
Division of Cardiovascular Pathophysiology, School of Medicine, University of Navarra, Pamplona, Spain.
Circulation. 2001 Jul 17;104(3):286-91. doi: 10.1161/01.cir.104.3.286.
We investigated whether serum concentration of carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type I synthesis, can be used to assess the ability of antihypertensive treatment to regress myocardial fibrosis in hypertensive patients.
The study was performed in 37 patients with essential hypertension and hypertensive heart disease. After randomization, 21 patients were assigned to losartan and 16 patients to amlodipine treatment. At baseline and after 12 months, right septal endomyocardial biopsies were performed to quantify collagen volume fraction (CVF) on picrosirius red-stained sections with an automated image-analysis system. Serum PIP was measured by specific radioimmunoassay. Nineteen patients in the losartan group and 11 in the amlodipine group finished the study. Time-course changes in blood pressure during treatment were similar in the 2 groups of patients. In losartan-treated patients, CVF decreased from 5.65+/-2.03% to 3.96+/-1.46% (P<0.01) and PIP from 127+/-30 to 99+/-26 microgram/L (P<0.01). Neither CVF or PIP changed significantly in amlodipine-treated patients. CVF was directly correlated with PIP (r=0.44, P<0.001) in all hypertensives before and after treatment.
These findings suggest that the ability of antihypertensive treatment to regress fibrosis in hypertensives with biopsy-proven myocardial fibrosis is independent of its antihypertensive efficacy. Our data also suggest that blockade of the angiotensin II type 1 receptor is associated with inhibition of collagen type I synthesis and regression of myocardial fibrosis in hypertensives. Thus, determination of serum PIP may be useful to assess the cardioreparative properties of antihypertensive treatment in hypertensives.
我们研究了I型前胶原羧基末端前肽(PIP)的血清浓度(I型胶原合成的标志物)是否可用于评估降压治疗使高血压患者心肌纤维化消退的能力。
该研究纳入了37例原发性高血压合并高血压性心脏病患者。随机分组后,21例患者接受氯沙坦治疗,16例患者接受氨氯地平治疗。在基线期和12个月后,进行右室间隔心内膜活检,使用自动图像分析系统在天狼星红染色切片上定量胶原容积分数(CVF)。通过特异性放射免疫测定法检测血清PIP。氯沙坦组19例患者和氨氯地平组11例患者完成了研究。两组患者治疗期间血压的时间进程变化相似。接受氯沙坦治疗的患者,CVF从5.65±2.03%降至3.96±1.46%(P<0.01),PIP从127±30降至99±26μg/L(P<0.01)。接受氨氯地平治疗的患者,CVF和PIP均无显著变化。治疗前后所有高血压患者的CVF与PIP均呈直接相关(r=0.44,P<0.001)。
这些发现表明,经活检证实有心肌纤维化的高血压患者,降压治疗使纤维化消退的能力与其降压疗效无关。我们的数据还表明,阻断1型血管紧张素II受体与抑制高血压患者I型胶原合成及心肌纤维化消退有关。因此,测定血清PIP可能有助于评估高血压患者降压治疗的心脏修复特性。