Pre-clinical studies suggest a protein, Agrin, could limit scarring and promote natural repair mechanisms after a heart attack
諸多臨床前研究暗示，Agrin這種蛋白能限制結疤，並促進心臟病發作後的自然修復機制。
圖1. 心臟病發作後的豬心電腦化影像。 與使用單劑量(中間)或雙劑量(右)Agrin處理的豬相較下，未經處理的豬心(左)疤痕組織(黑色)體積明顯較大 (圖援用自原文)
Heart disease is the number one cause of death in the world, surpassing all cancers combined. One of the major difficulties in coming up with new therapies lies in translating basic research findings, typically obtained with mice, into a treatment that works in humans. This gap can be filled by experimenting on pigs, whose hearts beat at a rhythm similar to that of humans and otherwise provide a faithful model – both size-wise and physiologically – of human cardiovascular function.
心臟病是世界上第一大死亡原因，超過所有癌症的總和。在想出新療法的主要困難之一，在於將通常使用小鼠獲得的基礎研究結果轉化成，在人類中起作用的一種療法。藉由使用心跳律動類似人類及，除此之外，在尺寸與生理上，也提供人類心血管功能之可靠模型的豬進行實驗，能填補此缺口。
Weizmann Institute of Science researchers, in close collaboration with a team from the Technical University of Munich, have now showed that the protein Agrin, previously found to renew damaged heart tissue in mice, promotes heart repair in pigs.
在與一支來自德國慕尼黑工業大學之團隊密切合作下，目前以色列魏茨曼科學研究所的研究人員們證實，先前在小鼠中，被發現更新受損心臟組織的Agrin蛋白，在豬中助長了心臟修復。
The researchers have also clarified Agrin’s mechanisms of action, which turned out to be similar in mice and pigs, indicating that it’s likely to work similarly in all mammals, including humans. These findings suggest that Agrin might serve as an effective therapy after heart attacks, promoting heart repair and helping to prevent chronic heart failure.
此些研究人員也已經闡明，在小鼠及豬中，Agrin經證實相似的作用機制。這顯示，在包括人類的所有哺乳動物中，起相似作用是可能的。此些研究發現暗示，Agrin可能充當一種，在心臟病發作後，助長心臟修復及有助於預防慢性心臟衰竭的有效療法。
Agrin is naturally present in the supporting heart cells in mouse and human fetuses, and in the hearts of newborn mice – that is, in settings where regeneration is possible, suggesting that it can play a role in heart muscle regeneration.
Agrin天然存在於小鼠與人類胎兒的支援性心臟細胞，及新生小鼠的心臟中。也就是說，可能存在於再生的環境中。暗示，其在心肌再生上，扮演一種角色。
Indeed, in previous research, a team headed by Prof. Eldad Tzahor of Weizmann’s Molecular Cell Biology Department had discovered that Agrin “unlocked” a renewal process in injured mouse hearts. To test whether this protein is likely to help heal human hearts, Tzahor established a collaboration with Prof. Christian Kupatt of the Technical University of Munich to study Agrin’s efficacy in pigs.
實際上，在先前由魏茨曼科學研究所分子細胞生物學系，Eldad Tzahor教授領導之團隊進行的研究已經發現，Agrin在損傷的小鼠心臟中“解鎖了”一種更新過程。為了驗證此種蛋白是否可能，有助於治癒人類心臟。Tzahor與慕尼黑工業大學的Christian Kupatt教授進行了合作，以研究Agrin在豬身上的功效。
Senior intern Dr. Kfir Baruch Umansky led the study, in which the researchers administered a synthetic form of human Agrin protein to the hearts of pigs that had been exposed to an injury simulating a heart attack.
資深駐院實習醫生Kfir Baruch Umansky博士，領導了這項研究。在該項研究中，此些研究人員對已經曝露於模擬心臟病發作受損傷的豬心臟，施予了合成形式的人類Agrin蛋白。
Working with Kupatt’s team in a hospital setting – and using clinical protocols and tools relevant to treating human patients – Umansky and colleagues found that a single dose of Agrin reduced scarring and improved heart function after the injury. The heart’s pumping capacity, measured by the volume of blood ejected with every beat, was significantly enhanced.
在醫院環境中，使用與治療人類病患有關的臨床治療方案及工具，與Kupatt團隊一起進行研究。Umansky及同僚們發現，在損傷後，單劑Agrin減少了結疤且改善了心臟功能。也就是，藉由測量隨著每次心臟跳動排出之血液量的心臟泵送能力，顯著增強。
In addition, the Agrin treatment prevented the rise of pressure in the heart’s main pumping chamber, which grows after a heart attack because the scarred heart becomes stiff and less effective at pumping. Since this parameter is a predictor of the subsequent risk of heart failure, the researchers suggest that Agrin can serve as a preventive therapy against this major complication of heart attacks.
此外，這種Agrin療法防止了，心臟病發作後。因為，結疤的心臟變得僵硬及較少泵血效能，而導致心臟主泵腔內壓力升高。由於此參數是隨後心臟衰竭風險的一種預測因子，此些研究人員暗示，Agrin可充當對抗心臟病發作之主要併發症的預防療法。
Focusing in greater detail on Agrin’s mechanism of action, the researchers found in both pig and mouse models that Agrin induces a broad range of repair processes, which is probably why a single dose of the protein produced potent effects lasting up to one month after the treatment.
更詳細著重Agrin的作用機制，在豬與小鼠模型中，此些研究人員發現，Agrin引發了廣泛的修復過程。這可能是在該種蛋白質單劑量治療後，為何產生維持長達一個月有效作用的原因。
The protein triggered a mild proliferation of heart muscle cells, which normally don’t divide, and, perhaps more importantly, protected them from dying, particularly in the border zone around the injury site, thus preventing the spread of scar tissue.
該種蛋白質觸發了，通常不分裂之心肌細胞的輕度增殖。更重要的或許是保護它們免於死亡，特別是在損傷部位周圍的邊界區域。因此，防止了結疤組織的擴散。
In addition, Agrin beneficially altered the immune response to the injury within the heart muscle: It curbed inflammation by reducing the activation of immune cells called macrophages that are responsible for the early release of inflammatory substances. Not only that, the scientists found that Agrin protected existing blood vessels within the heart muscle and stimulated the growth of new ones.
另外，Agrin有益地改變了，對心肌內損傷的免疫反應：其藉由減少，導致初期釋出發炎物質，被稱為巨噬細胞之免疫細胞的活化，來抑制發炎。不僅如此，此些科學家也發現，Agrin保護了心肌內現有血管，且刺激了新血管的成長。
In the course of the study, the method that worked best for delivering Agrin to the injured pig heart was to inject it into the coronary artery using the same type of catheter that is generally used in angioplasty to widen obstructed arteries. This suggests that patients undergoing angioplasty could have a dose of Agrin administered at the same time.
在該項研究過程中，起最佳將Agrin遞送到受損豬心臟的方法，是使用通常在血管成形術中，被用來擴張阻塞之動脈的同類型導管，來將其注入冠狀動脈中。這暗示，經受血管成形術治療的病患，同時能被施予一劑Agrin。
Agrin’s effectiveness in such large animals as pigs, together with the ease of delivery, could pave the way to its use in human patients. Scarring and loss of heart function are prevalent after a heart attack, and the study’s findings suggest we may finally have a way to limit and possibly even reverse the damage, improving the outcome of heart attacks and perhaps averting their complications.
Agrin在諸如豬之大型動物中的功效，連同容易遞送。這可能為其使用於人類病患中鋪路。在心臟病發作後，結疤及心臟功能喪失是普遍的，而該項研究的此些發現暗示，咱們最終可能擁有一種，限制及甚至可能扭轉損傷的方法，來改善心臟病發作的後果，及或許避免其諸多併發症。
“The road from basic research to the clinic is long and often bumpy, so our study in pigs provides a critical step in this direction,” Tzahor says. This study was made possible, in part, by a new program that aims to bridge the gap between promising basic science breakthroughs at the Institute and commercial application. Called IDEA (Innovation, Development, Enhancement and Acceleration), it is an initiative of Yeda, Weizmann’s technology transfer arm.
Tzahor宣稱：「從基礎研究到臨床是一條漫長，且往往坎坷的道路。」該項研究部分是由旨在填補，於研究所諸多有指望之基礎科學突破與商業應用間之間隙的一項新計劃，使之實現的。它被稱為IDEA(創新、發展、增強及加速)，是魏茨曼技術轉移部門Yeda的一項倡議。
原文網址：https://wis-wander.weizmann.ac.il/life-sciences/potential-heart-repair-protein-advances-new-stage
翻譯：許東榮
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