Khasa Yogender Pal
a Department of Microbiology , University of Delhi South Campus , New Delhi , India.
Bioengineered. 2017 Jul 4;8(4):331-358. doi: 10.1080/21655979.2016.1229718. Epub 2016 Oct 3.
Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.
由于酗酒、肥胖、高血压、血脂升高、糖尿病以及与年龄相关的风险,心血管疾病在全球范围内呈上升趋势。在早期,使用经典的抗血小板和抗凝疗法并结合手术干预有助于清除血栓。然而,链激酶和尿激酶的发现开创了将这些酶用作溶栓剂以降解纤维蛋白网络的方法,但存在全身出血问题。第二代纤溶酶原激活剂如茴香酰化纤溶酶原链激酶复合物和组织纤溶酶原激活剂的开发部分控制了这个问题。第三代分子,主要是组织纤溶酶原激活剂变体,表现出稳定性、安全性和有效性提高以及纤维蛋白特异性增强等理想特性。纤溶酶变体作为直接溶栓剂生产,是一种未来的方法,可使用脂质体技术靶向递送这些药物。来自微生物、植物和动物来源的新型分子因其安全性和易于给药而展现出直接溶栓剂的未来前景。