1.TGF- β1 of cardiac tissue and ventricular remodeling in rats with acute myocardial infarction
Ying LIU ; Yuhua LIAO ; Xiang CHENG ; Bin LI ; Hongxia GE ; Ling ZHANG ; Zhangqiang GUO
Chinese Journal of Pathophysiology 2005;21(12):2305-2309
AIM: To explore the molecular mechanisms about fibrosis and transforming growth factor (TGF) - β1 as well as inflammation in rats heart after acute myocardial infarction (AMI). METHODS: AMI model in rats was produced by left coronary artery ligation. Samples of rat cardiac tissue were collected at the end of 1 week, 4 weeks and 8 weeks. Hemodynamics had been performed before rats were sacrificed. Reverse transcription polymerase chain reaction (RT- PCR) and immunohistochemical methods were used to analyze mRNA expression and protein production of TGF- β1, respectively. Hydroxyproline was determined by chloramines T method. HE staining was resorted to analyze pathological myocardium after AMI. RESULTS: There were remarkable differences in hemodynamics between AMI groups and sham group (P<0.01). Compared with sham group, TGF-β1mRNA expression and protein production and hydroxyproline quantification were enhanced greatly. Among them, the levels of TGF -β1 and hydroxyproline at 1 week were higher than those at 4 weeks or 8 weeks. A positive correlation between TGF- β1 protein and hydroxyproline was presented (r=0.75 - 0.99, P<0.05). In microscope, leucocytes infiltrated significantly in the infarcted and border myocardium at 1 week after AMI, and were rarely seen at 4 weeks and 8 weeks. TGF - β1 protein were detected in cytoplasm of cardiac myocyte and leucocytes at 1 week, and at 4 and 8 weeks in myofibroblast and interstitial. CONCLUSIONS:TGF- β1 is upregulated and found in cytoplasm of cardiac myocyte and leucocytes as well as myofibroblast in heart after AMI,which is associated with dynamic changes of hydroxyproline content and inflammation. TGF - β1 is showed to play an important role in myocardial inflammatory repair and ventricular remodeling after AMI.
2.Significance of the imbalance of Th1/Th2 function after acute myocardial infarction
Xiang CHENG ; Yuhua LIAO ; Hongxia GE ; Bin LI ; Ying LIU ; Zhangqiang GUO ; Ling ZHANG
Chinese Journal of Pathophysiology 1999;0(09):-
AIM: The study explored the significance of the imbalance of Th1/Th2 function after acute myocardial infarction (AMI). METHODS: Peripheral blood mononuclear cells from 33 AMI patients, 22 unstable angina (UA) patients and splenocytes from 35 AMI rats were collected. Cytokine-producing Th cells were monitored by 3-color flow cytometry after stimulated with phorbol myristate acetate (PMA) and ionomycin. IFN-? and IL-4 mRNA in the rat myocardium and chemokine receptors CCR3, CCR5 and CXCR3 mRNA on the surface of rat T lymphocytes after AMI were measured by RT-PCR. RESULTS: Th1 associated cytokine IFN-? significantly increased in patients with AMI and UA within 24 hours after the onset of symptom. the high ratio of IFN-?-producing T cells lasted short in patients with UA and recovered 1 week after the onset. In AMI patients, the high ratio of IFN-?-producing T cells could be examined 1 week and even 1 month after the onset. There was no significant difference on the frequencies of IL-4-producing peripheral T cells between each group. 1 week, 2 weeks and 1 month after AMI, IFN-? mRNA increased in the myocardium of rats, but there was no significant change on cytokine-producing Th cells and chemokine receptors on the surface of rat T lymphocytes. CONCLUSIONS: The Th1/Th2 functional imbalance and up-regulation of Th1 cell-functions exist after AMI and perhaps participate in the onset of AMI. Th1/Th2 functional imbalance may participate in the immune-mediated myocardial injury and ventricular remodeling after AMI as one of the pathogenesises of autoimmune disease.
3.Changes of cytokine and collagen in the myocardial remodeling after acute myocardial infarction in rats
Zhangqiang GUO ; Yuhua LIAO ; Xiang CHENG ; Bin LI ; Hongxia GE ; Ying LIU ; Ling ZHANG ; Min WANG ; Heping GUO
Chinese Journal of Pathophysiology 2000;0(12):-
AIM: To clarify the relationship between the cytokine and collagen in myocardial remodeling after acute myocardial infarction(MI) in rats.METHODS: In MI group,Wistar rats were undergone acute myocardial infarction by ligation of the anterior descending coronary artery.Sham operation was made in rats as control.The mRNA expression of collagen and cytokines such as TNF-? and TGF-?_1 in infract and non-infarct region of left myocardium were detected by RT-PCR at different time point(3 d,1 and 4 weeks).RESULTS: Collagen type Ⅰ and Ⅲ elevated as well as the TNF-? and TGF-?_1 in the MI group at 3th day.Expression of collagen type Ⅰ and Ⅲ were higher in the infarct region than that in the non-infarct region even at 4 weeks.TNF-? and TGF-?_1 peaked at 1 week and declined gradually to the baseline,which was still higher than those in control group(P
4.The dynamic change of TGF-beta1 in the myocardial remodeling of rat after myocardial infarction.
Zhangqiang, GUO ; Yuhua, LIAO ; Xiang, CHENG ; Bin, LI ; Ying, LIU ; Hongxia, GE ; Ling, ZHANG ; Min, WANG ; Heping, GUO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2006;26(4):417-20
To observe the dynamic changes of the TGF-beta1 expressed in the infarct and non-infarcted region of rat heart during the ventricular remodeling (day 3, 7, 28, 180), myocardial infarction rat model was made and relationship between the cytokine and indicator of myocardial remodeling was analyzed. After the detection of hemodynamic parameter was performed by the Powerlab devices, the size of myocardial infarction and the morphology change was detected by TTC and HE, respectively. The relative levels of mRNA of TGF- beta1, collagen type I, III, and fetal gene beta-MHC were detected by RT-PCR. The distribution of TGF- beta1 protein in the myocardium was detected by immunohistochemistry. The results showed that the size of infarction was higher than that of the sham operated groups in the infarcted group (44.5 +/- 0.5 vs 0). The difference in hemodynamic parameters between the infarcted group and sham operated group was significant (P < 0.01). HE staining showed that inflammatory cells were accumulated in the infarcted region at the beginning of the 3rd day, which lasted 4 weeks. Then, it decreased gradually. beta-MHC in the non-infarcted region rose from the 3rd day, reaching its peak at the 4th week, and it decreased gradually. The ratio of the collagen type I/III showed similar changes as compared with the sham operated groups (P < 0.01). And the relative mRNA levels in the non-infarcted group were significantly higher than that in the infarcted and sham operated group (P < 0.01) at day 180. Linear regression analysis indicated that the TGF-beta1 was positively correlated with the ventricular remodeling. It was concluded that the cytokine TGF-beta1 participates in the process of the myocardial remodeling, which could be a strategy in the interference of myocardial remodeling.
5.The Dynamic Change of TGF-β1 in the Myocardial Remodeling of Rat after Myocardial Infarction
Zhangqiang GUO ; Yuhua LIAO ; Xiang CHENG ; Bin LI ; Ying LIU ; Hongxia GE ; Ling ZHANG ; Min WANG ; Heping GUO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2006;26(4):417-420
To observe the dynamic changes of the TGF-β1 expressed in the infarct and non-infarcted region of rat heart during the ventricular remodeling (day 3, 7, 28, 180), myocardial infarction rat model was made and relationship between the cytokine and indicator of myocardial remodeling was analyzed. After the detection of hemodynamic parameter was performed by the Powerlab devices, the size of myocardial infarction and the morphology change was detected by TTC and HE, respectively.The relative levels of mRNA of TGF- β 1, collagen type Ⅰ, Ⅲ, and fetal gene beta-MHC were detected by RT-PCR. The distribution of TGF- β1 protein in the myocardium was detected by immunohistochemistry. The results showed that the size of infarction was higher than that of the sham operated groups in the infarcted group (44.5±0.5 vs 0). The difference in hemodynamic parameters between the infarcted group and sham operated group was significant (P<0.01). HE staining showed that inflammatory cells were accumulated in the infarcted region at the beginning of the 3rd day,which lasted 4 weeks. Then, it decreased gradually. β-MHC in the non-infarcted region rose from the 3rd day, reaching its peak at the 4th week, and it decreased gradually. The ratio of the collagen type Ⅰ/Ⅲ showed similar changes as compared with the sham operated groups (P<0.01). And the relative mRNA levels in the non-infarcted group were significantly higher than that in the infarcted and sham operated group (P<0.01) at day 180. Linear regression analysis indicated that the TGF-β1 was positively correlated with the ventricular remodeling. It was concluded that the cytokine TGF- β1 participates in the process of the myocardial remodeling, which could be a strategy in the interference of myocardial remodeling.