Ongoing basic molecular analyses are being performed in mice, and a simple long-surviving murine model of myocardial infarction (MI) would be very useful in this regard. Although a few studies have induced MI in mice by coronary artery ligation, the induction involves a complex technique and has a relatively high mortality rate. In addition, the identification of the basic pathological sequence is essential to the interpretation of experimental results. We developed a simple technique for the induction of MI in mice and examined qualitative and quantitative conventional microscopic findings during the pathological evolution over a 28-day observation period. Male BALB/c mice weighing approximately 25-30 g were anesthetized and then ventilated with a positive pressure ventilator. The heart was exposed by thoracotomy. Left coronary artery occlusion was performed by thermocoagulation using a thermocoagulation knife at the level of the tip of the left atrium. After establishing this surgical method, we used it to induce MI in 71 mice. The operative and postoperative mortality rates of this model were 5.6% (4/71) and 12.6% (9/71), respectively. In 3 (5.2%) of the 58 surviving mice, the area of infarct was not sufficient. The infarct area in the remaining 55 mice was 40 +/- 9% of the entire perimeter of the left ventricle. Conventional microscopic examinations with hematoxylin-eosin and Masson-trichrome staining disclosed that all of the characteristic histopathological features of MI occurred 1-2 days earlier than those in rats. Our surgical technique provides a sufficient infarct area, with an acceptable mortality rate. The present study clarified the histopathological sequence in this long surviving murine MI model.
SUMMARYThe type X\'II collagen al chain has been identified as a component of the type I hemidesmosome, and is thus thought to play a role in extracellular matrix ECM maintenance and signal transduction between the cell and the EC\I. We examined the expression of type XVII collagen al chain mRNA in the mouse heart by Northern blot analysis and determined the sequential changes of its expression in different developmental stages of the heart using the reverse transcriptase-polymerase chain reaction (RT-PCR) method..Vorthem blotting: Total RNA was extracted from 10 adult mouse hearts by the guanidine/cesium method. Hybridization was performed with mouse cDNA for a1 XVIL collagen. RT-PCP,• Total RNA was extracted from 7 embryos . 4 neonates and 8 adult mice. Reverse transcription was performed using oligo-dT primer and \I\ILV. Amplification was carried out in a1 XVIIi collagen and glyceraldehyde 3-phosphate dehvdrogenase (GAPDH). GAPDH served as an internal control. Northern blotting revealed a 5.6 kb signal that was identical to that of the a1 XVII) of skin and transformed keratinocyte reported previously. The sequences of the PCR products were also identical to those reported. The normalized expression ratios of al XVII) were 0.91 ± 0.20 in the embryonic heart, 0.36 ± 0.20 in the neonatal heart and 0.96 ± 0.21 in the adult heart. In conclusion, we identified the expression of type XVII collagen al chain mRNA in the mouse heart, suggesting that the type I hemidesmosome is located in the heart. The results of the RT-PCR at different developmental stages of the heart suggest that type XVII collagen contributes not only to cardiogenesis in the embryonic stage but also to maintenance of architecture and function in the adult heart. (Jpn Heart J 1998; 39: 211-220)
SUMMARYFibrillar collagen plays an essential role in ventricular remodeling, which is a major prognostic factor in various heart diseases. Inflammatory cytokines, including tumor necrosis factor α (TNFα), have been reported to play a role in various heart diseases and OPC-8212, a quinolinone derivative, has been demonstrated to reduce TNFα production. No studies have examined the effects of OPC-8212 on collagen metabolism in connection with inflammatory cytokine and growth factors. Using lipopolysaccharides as a tool to enhance TNFα, we examined the effects of OPC-8212 on the expression of type III collagen mRNA [α1(III)] in cultured neonatal rat cardiac fibroblasts. We also measured the concentration of TNFα and transforming growth factor β (TGFβ) in the cultured medium. Northern blot analysis revealed that LPS reduced the expression of α1(III) mRNA, and OPC-8212 counteracted this reduction (on average 25% above the reduced level by LPS stimulation). LPS enhanced the TNFα concentration in the medium, and OPC-8212 inhibited this enhancement. LPS increased the TGF-β1 concentration in the cultured medium, while OPC-8212 did not affect this increase. In summary, OPC-8212 counteracted the reduction in type III collagen mRNA expression by LPS accompanied by suppression of the increase in TNFα. (Jpn Heart J 2001; 42: 125-134)
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