鬱血性心衰竭是已開發國家排名第一的死因。造成心衰竭最主要的病因是冠狀動脈阻塞所導致的心肌壞死。因此，增進心肌血管新生的治療可能可以提供有效的治療方法以避免心衰竭的產生。
血管新生(Neovascularization)是一個十分複雜的生理過程。血管內皮生長因子(Vascular Endothelial Growth Factor, VEGF)在血管新生的啟動與初始過程中扮演必要的角色。然而，直接注射VEGF蛋白或是攜帶有VEGF基因載體進入心臟的臨床試驗都沒有能夠提供病患助益，可能是因為VEGF過量或是未能達成控制性緩慢釋放所致。目前已知有效的血管新生需要非常嚴密的控制微環境中的VEGF表現，VEGF含量太多或太少均無效。此外，凝血脢調節素(Thrombomodulin, TM)第二與第三結構域(TM Domain 2 and 3, TMD23)也已被證明可能俱有血管新生的效果。因此，我提出一個假設，以自組裝胜奈米纖維 (Peptide Nanofibers, NF)的控制性心肌內VEGF與TMD23緩慢釋放可以在大鼠心肌梗塞模式中促進血管新生，並進而改善心臟功能。
我以雄性200-250克重的Sprague-Dawley大鼠進行心肌梗塞的動物模式，將其冠狀動脈左前降枝進行永久性結紮以引發心肌壞死，接著馬上在壞死心肌與其周邊注射總共100ul的NF與其所攜帶不同劑量的VEGF或 TMD23，再利用心臟超音波在手術後第一天與第二十一天進行左心室收縮分率(Ejection Fraction, EF%)的測定。我的結果顯示EF%在只有施打NF組在術後第二十一天有明顯的改善。但是，VEGF的投遞，不管是否透過奈米纖維，都無助於心臟功能。很驚訝的是，心臟功能在TMD23劑量100或1000 ng/ml都有明顯的改善，TMD23劑量10 ng/ml則無助於心臟功能。有趣的是，同時施打NF 與TMD23並不能產生更大的效果。利用微血管染色密度分析，我也發現TMD23劑量100與1000 ng/ml都可以明顯增加心肌梗塞邊緣的血管密度。這些結果顯示，胜奈米纖維與TMD23心肌內注射可能有助於心肌梗塞後心臟的重塑(Remodeling)與重建(Repair)。本研究未來的計畫將著重在探討上述兩者對心臟助益的背後機制為何，同時探討這樣的治療方法是否在大動物的心肌梗塞模式也能被證明俱有療效。

Congestive heart failure is the leading cause of death in developed countries. The predominant cause of heart failure is myocardial loss due to coronary artery disease. Therefore, therapies improving myocardial neovascularization may provide promising approaches to prevent heart failure.
Vascular endothelial growth factor (VEGF) plays an essential role in controlling neovascularization program. However, until recently have clinical trails using direct intramyocardial injection of human VEGF protein (hrVEGF165) or vectors such as plasmids carrying VEGF gene transfer failed to prove benefits for patients. This is possibly due to an uncontrolled release or an overdose of VEGF by these approaches, given that for effective neovascularization the expression of VEGF needs to be tightly regulated in the microenvironments. Besides, thrombomodulin (TM) domain 2 and 3 (TMD23) has been identidied as a novel angiogenic factor with potentials for therapeutic angiogenesis. Accordingly, I hypothesize that controlled intramyocardial delivery of hrVEGF165 or TMD23 using peptide nanofibers for slow release may improve therapeutic neovascularization in a rat model of myocardial infarction (MI).
MI was created in 200-250g male Sprague-Dawley rats through permanent ligation of left anterior descending coronary artery, immediately followed with intramyocardial injections of 100 μl of hrVEGF165 or TMD23, with or without peptide nanofibers (NF), into the border zones and infarcted areas. The ejection fraction (EF%) was measured at day 1 and day 21 after surgery using echocardiography. The results showed that the ejection fraction was improved in groups with NF injection at day 21. However, there was no significant difference of EF% among VEGF groups with or without nanofibers, no matter in the 10, 100 or 1000 ng/ml dose of VEGF used. Surprisingly, injection of TMD23 alone showed a significant improvement of cardiac functions at the dose of 100 or 1000 ng/ml, but not at the low dose of 10 ng/ml, with or without nanofibers. The capillary density in the peri-infarct areas was also increased by TMD23 injection, with no difference between the groups with or without nanofibers co-injection.
Together these results suggest that NF itself or TMD23 injection may have beneficial effects on cardiac remodeling or cardiac repair following acute infarction. Future studies will be carried out to explore the mechanisms underlying these cardiac benefits induced by NF or TMD23 injection and to examine if the same cardiac benefits can be observed using large animals such as pigs.

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