既存薬の新規使用で心臓発作リスクを大幅に低減できる可能性(Novel Use of Existing Drug Could Significantly Cut Heart Attack Risk)

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2024-06-18 ジョージア工科大学

心臓発作はアメリカで最も多い死因であり、通常の治療法は血栓の分解を目指しますが、ジョージア工科大学の研究者は血栓の形成そのものを防ぐ方法を発見しました。この薬は血栓形成を完全に抑制し、出血リスクを増やさないことが動物実験で示されています。この薬は既に他の用途で広く使用されており、患者は新薬のFDA承認を待つことなく、早期に恩恵を受けられます。研究成果は「N-Acetyl Cysteine Prevents Arterial Thrombosis in a Dose-Dependent Manner In Vitro and in Mice」として発表されました。von Willebrand因子(VWF)を標的とするこの薬は、VWFが血小板を捕捉するのを防ぎ、血栓の迅速な形成を阻止します。研究チームは、既存のN-アセチルシステイン(NAC)を使用し、血栓形成を防ぐ効果を確認しました。NACは心臓発作後の再発予防に有望で、将来的には経口投与も可能とされます。心臓発作や脳卒中の予防に留まらず、塞栓症などにも適用可能です。

<関連情報>

N-アセチルシステインがマウスとインビトロで用量依存的に動脈血栓症を予防する N-Acetyl Cysteine Prevents Arterial Thrombosis in a Dose-Dependent Manner In Vitro and in Mice

Christopher A. Bresette,Katrina J. Ashworth,Jorge Di Paola andDavid N. Ku
Arteriosclerosis, Thrombosis, and Vascular Biology  Published21 Dec 2023
DOI:https://doi.org/10.1161/ATVBAHA.123.319044

Abstract

BACKGROUND:
Platelet-rich thrombi occlude arteries causing fatal infarcts like heart attacks and strokes. Prevention of thrombi by current antiplatelet agents can cause major bleeding. Instead, we propose using N-acetyl cysteine (NAC) to act against the protein VWF (von Willebrand factor), and not platelets, to prevent arterial thrombi from forming.

METHODS:
NAC was assessed for its ability to prevent arterial thrombosis by measuring platelet accumulation rate and occlusion time using a microfluidic model of arterial thrombosis with human blood. Acute clot formation, clot stability, and tail bleeding were measured in vivo with the murine modified Folts model. The effect of NAC in the murine model after 6 hours was also measured to determine any persistent effects of NAC after it has been cleared from the blood.

RESULTS:
We demonstrate reduction of thrombi formation following treatment with NAC in vitro and in vivo. Human whole blood treated with 3 or 5 mmol/L NAC showed delayed thrombus formation 2.0× and 3.7× longer than control, respectively (P<0.001). Blood treated with 10 mmol/L NAC did not form an occlusive clot, and no macroscopic platelet aggregation was visible (P<0.001). In vivo, a 400-mg/kg dose of NAC prevented occlusive clots from forming in mice without significantly affecting tail bleeding times. A lower dose of NAC significantly reduced clot stability. Mice given multiple injections showed that NAC has a lasting and cumulative effect on clot stability, even after being cleared from the blood (P<0.001).

CONCLUSIONS:
Both preclinical models demonstrate that NAC prevents thrombus formation in a dose-dependent manner without significantly affecting bleeding time. This work highlights a new pathway for preventing arterial thrombosis, different from antiplatelet agents, using an amino acid derivative as an antithrombotic therapeutic.

既存薬の新規使用で心臓発作リスクを大幅に低減できる可能性(Novel Use of Existing Drug Could Significantly Cut Heart Attack Risk)

有機化学・薬学
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