Spontaneous Coronary Artery Dissection (SCAD)
Spontaneous coronary artery dissection (SCAD), a rare idiopathic disease, predominantly occurs in young and otherwise healthy women. During the last 10 years, SCAD has been recognized as an important cause of myocardial infarction. In the drug development of rare heart conditions such as SCAD, breakthroughs come only with expertise and resources. Protheragen is among the leading research services providers with full capability of drug discovery and can provide comprehensive preclinical discovery and development services.
Introduction to Spontaneous Coronary Artery Dissection (SCAD)
Spontaneous coronary artery dissection (SCAD) is an etiology of dissecting lesions in epicardial coronary arteries not related to iatrogenic or traumatic causes or atherosclerosis. Unlike intraluminal thrombosis or plaque rupture leading to acute coronary syndrome (ACS), the mechanism of ACS in SCAD is myocardial ischemia because of coronary luminal obstruction by hematoma following intimal tear or intramural hematoma (IMH), where false lumen has developed.
Fig.1 SCAD-associated conditions and SCAD trigger factors. (Hayes, S. N., et al., 2020)Pathogenesis of Spontaneous Coronary Artery Dissection (SCAD)
SCAD is probably modulated by a variety of factors, such as sex, hormonal swings, arteriopathies, genetic predisposition, and psychological and environmental stressors. SCAD is an acute coronary syndrome precipitated by hematoma formation within the tunica media resulting in separation of the intima from the underlying vessel, which compresses the true lumen, thereby causing ischemia and AMI. Two theories have been advanced to explain the pathophysiology: in the "inside-out" theory, blood enters the subintimal space from the true lumen after a true endothelial-intimal disruption or "flap" has developed; in the "outside-in" theory, a hematoma develops in the media, presumably as a result of the destruction of transversing microvessels.
Fig.2 Angiographic identification of SCAD. (Hayes, S. N., et al., 2020)Therapeutics Development for Spontaneous Coronary Artery Dissection (SCAD)
| Drug Name | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|
| Aspirin | Preventing ischemia through irreversible inhibition of COX-1 and thus inhibiting platelet aggregation, and by so doing decreasing the thrombus. | COX-1 | Phase IV |
| Clopidogrel | By preventing platelet aggregation via the irreversible binding of the P2Y12 receptors on platelets, fewer thrombus form along the site of arterial dissection. | P2Y12 Receptor | Phase IV |
| Ramipril | Reducing blood pressure by inhibiting angiotensin-converting enzymes helps reduce arteriole wall stress and minimize arteriolar damage. | ACE | Phase IV |
| Rosuvastatin | Reducing the LDL cholesterol can reduce the risk for future cardiovascular events. | HMG-CoA, hERG | Phase IV |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.
Our Services
Throughout your drug development, whether it's cutting-edge diagnostics, trail-blazing therapeutics, or advanced disease models, we are here to help you speed up your R&D and get solutions that work. Using professional approaches, our full range of preclinical services can help develop potential therapeutics through rigorous testing for safety and effectiveness, before advancement to additional trials.
Therapeutic Development Services
Animal Model Development for SCAD
In advancing drug discovery and research, it is important to establish an animal model for SCAD to gain further insights into the pathogenesis of the disease and identify potential targets for therapy. We understand the value of accurate and dependable models and provide customized animal model development services that fit your unique project to expedite your R&D and increase the possibility of successful therapies.
Using β-aminopropionitrile (BAPN) induced hypertension, generated arterial dissections similar to SCAD-like lesions.
Animal models with mutations in the genes for polypeptides of type III collagen (COL3A1) have vasculature which is fragile and prone to spontaneous dissection.
SCAD-like lesions can be mechanically created by injuring the left anterior descending artery (LAD) with a stiff guidewire.
Recognizing the challenges of rare cardiovascular condition therapeutics, Protheragen provides bespoke and flexible services to address individual project requirements. By combining the strength of a diverse team of scientists with cutting-edge technologies, we have the greatest ability to perform all kinds of pharmacokinetic studies and drug safety evaluations. Working with us, you get an experienced, forward-thinking, leading-edge technical support provider. Contact us today to see how we could address your drug discovery and development projects.
Reference
- Hayes, Sharonne N et al. "Spontaneous Coronary Artery Dissection: JACC State-of-the-Art Review." Journal of the American College of Cardiology 76.8 (2020): 961-984.
For research use only, not for clinical use.