What is Myocardial Infarction?
Myocardial infarction (MI) is defined as clinical evidence of myocardial necrosis consistent with myocardial ischemia. Risk factors include smoking, high blood pressure, excessive alcohol intake, among others. Usually, the underlying mechanism of an MI is the complete blockage of a coronary artery due to occlusive thrombosis, which is caused by atherosclerotic plaque rupture or restenosis. In view of the critical role of thrombosis in the pathogenesis of MI, research efforts have been aimed at the discovery and development of safe and effective antithrombotic drugs for clinical use.
Complement System & Coagulation System
The complement system is a part of the innate immune system that may be activated through three pathways: the classic, the alternative, and the lectin pathways. The coagulation system is responsible for maintaining the thrombohaemmorhagic balance in the body by complicated interactions between coagulation and the fibrinolytic system as well as platelets and vessel wall. A number of recent studies have shown direct interactions between the two systems, among them are links between coagulation factors and mannan (or mannose)-binding lectin (MBL) associated serine proteases (MASPs) of the complement lectin pathway.
Fig. 1 The schematic diagram of myocardial infarction.1
The Role of MASP-1 in MI
MASP-1 and MASP-2 have been shown to contribute to in vitro fibrin clot formation. First evidence for an in vivo role of MASP-1 in coagulation has been recently documented in a study demonstrating that mice lacking MBL or MASP-1 have a prolonged bleeding time following tail-tip excision. Furthermore, it has been recently exhibited in a mouse model of FeCl3-induced intra-arterial thrombogenesis, that MASP-1 plays a key role in thrombus formation in vivo. Clinically, a study reported that MASP-1 levels were observed to be the highest in patients with subacute MI patients among the measured MASPs and MAp44 levels, indicating that MASP-1 may be novel targets in the diagnosis, prevention, and treatment of MI.
MI Treatment by Complement Inhibition
For the treatment of MI, many studies have reported the beneficial use of complement inhibition targeting the lectin pathway components. For instance, monoclonal antibodies against rat MBL are discovered to be capable of protecting rats against myocardial damage. However, no human studies have found reduced myocardial ischemia/reperfusion injury by lectin pathway inhibition. As a result, studies aiming at developing novel therapeutics targeting at lectin pathway component-MASP-1 might be very promising and attractive.
As a first-class company in the biopharmaceutical field, Creative Biolabs is a trusted partner and expert in the complement-targeted drug discovery and development aided by advanced Complement Therapeutics Platform. We offer a full range of drug discovery services for subacute myocardial infarction based on the complement system. Please contact us for detailed information.
Reference
1. From Wikipedia: By Blausen Medical Communications, CC BY-SA 3.0， https://commons.wikimedia.org/wiki/File:Blausen_0463_HeartAttack.png
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Questions & Answer
A: Animal models, such as mice or rats, are often used to study complement therapeutics in subacute myocardial infarction. Ischemia-reperfusion models and permanent coronary ligation models are commonly employed.
A: Promising experimental drugs include complement inhibitors like anti-C5 monoclonal antibodies or small molecules targeting C3 activation. Additionally, strategies involving gene therapy to modulate complement regulation are being explored.
A: Researchers typically assess the effectiveness of complement therapeutics by evaluating parameters such as infarct size, cardiac function, inflammation markers, and tissue damage in experimental models.
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