根據統計，心臟衰竭在已開發國家中高居十大死因的第一名，而造成心臟衰竭的主要原因是來自冠狀動脈心臟病 （即心肌梗塞）。心肌梗塞會造成心肌細胞因缺血而死亡，以致心室功能不全，最後導致心臟衰竭。由於心臟在成人體內幾乎是無法再生的器官，因此心臟再生醫學的主要目的即是保護存活的心肌細胞免於死亡，同時希望也能夠使心臟再生新的細胞，減低急性或慢性的心肌損壞，以減少心臟病患的死亡。
Survivin 是一個只會在胚胎時期以及癌細胞中大量表現的蛋白質，在正常成人體內已分化的器官並不會表達。研究顯示，survivin 具有抗細胞凋亡與促進細胞有絲分裂的雙重功能，但目前對survivin 於心臟方面的研究仍十分有限。我們先前的研究發現心臟專一性缺乏survivin 的基因剃除小鼠具有心臟表型的缺失，有早期死亡的趨勢，與較差的心臟功能。進一步探討原因發現可能是由於心臟細胞的分裂比率較正常小鼠來得低的緣故。根據這個重要的發現，我假設利用survivin 可以保護心肌細胞甚至修復受損的心臟。
在本研究中，我首先探討survivin 在正常發育過程的胚胎以及出生後大鼠的心臟中的表現情形，結果發現survivin 在胚胎中以及出生後14 天之內的心的中皆有表達，且其表現量隨著出生天數增加而下降。我也利用動脈節紮的方法製造大鼠的心肌梗塞，之後在不同的時間點分析survivin 的表現情形，結果發現survivin 在實驗組中的表現量在術後七天之內有重新被誘導的現象，但在術後十四天之後及對照組中皆無法偵測到survivin 的蛋白質表現。因為先前的實驗結果顯示survivin 能夠促進體外心肌細胞的DNA 含量，也可抑制藥物所誘導的心肌細胞死亡，因而我也探討了survivin 在心肌細胞中是透過怎樣的機制執行它的功能。利用流式細胞儀分析，我發現過度表現survivin 的心肌細胞進入有絲分裂期的比例較高，調控細胞分裂的重要分子Aurora B 的表達也有上升的趨勢；但在探討survivin 對於抗細胞凋亡蛋白caspase-3 的實驗中，卻未發現對caspase-3 的表達有任何明顯的影響。因此，我未來的研究重點除了繼續探討survivin 對於心肌細胞分裂的分子機制之外，也將先釐清心肌細胞死亡的模式，以選定特定的細胞凋亡分子進行研究。另一方面，我也將著手進行動物實驗，探究survivin 是否可以在心肌梗塞之後保護心臟的功能，同時也促進受損的心臟修復以及再生。

The dominant cause of heart failure is regional loss of myocardium due to coronary artery disease. In the ischemic region, cardiomyocytes undergo necrosis and apoptosis
and are not adequately replaced, leading to scar formation and ultimately, loss of ventricular function. Myocardial regeneration aims at protecting cardiomyocyte death and regrowing new cardiomyocytes to improve cardiac performance. However, this enthusiasm is frequently challenged by the fact that the mammalian heart, a terminally differentiated organ, is incapable of spontaneous regeneration.
Survivin is the smallest member of the inhibitor of apoptosis protein (IAP) family. Previous studies have shown that survivin is a key modulator of apoptosis inhibition and cell cycle progression in cancer cells. However, the function of survivin in the heart is largely unknown. Through a cardiac specific survivin deletion using Cre-Lox system, we have recently reported that survivin may modulate cardiac function in mice through regulating the amount of cardiomyocytes. In vitro, adenoviral overexpression of survivin also protects cardiomyocytes from apoptosis, induces DNA synthesis and promotes cell cycle progression. Using immunohistochemistry and Western blotting, I found that survivin was highly expressed in the developing mouse hearts but not in the hearts 14 days after birth or older. Interestingly, I also detected the re-activation of survivin in the peri-infarcted myocardium following experimental myocardial infarction. To explore the underlying mechanisms of survivin in regulating cardiomyocyte mitosis and apoptosis, I investigated key molecules controlling cardiomyocyte growth. I found that the mRNA level of Aurora-B and cyclin-A, among more than 10 genes examined, was significantly increased in cultured cardiomyocytes after adenoviral overexpression of survivin for 24 or 48 hours. Together these results suggest a true potential of manipulating survivin for cardiac protection and possibly, cardiac regeneration.

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