Acute Aortic Dissection

Acute aortic dissection is an uncommon but life-threatening condition that carries a mortality rate of 1-2% per hour after the initiation of symptoms in individuals without therapy. Thus, prompt and accurate diagnosis of such individuals is important to improve the chance of their survival and avoid severe complications. At the forefront of rare cardiovascular disease research service providers, Protheragen offers comprehensive drug research and development services to expedite your discoveries from bench to bedside. Our vision is to bring you innovative solutions across all aspects of the acute aortic dissection.

Introduction to Acute Aortic Dissection

The most common of these life-threatening aortic conditions is aortic dissection, occurring at a rate of approximately 3 cases per year per 100,000 individuals. Warning symptoms of an acute aortic dissection, such as acute chest pain, hypotension, or syncope, therefore mimic acute myocardial infarction or pulmonary embolism.

Old age, male sex, prolonged arterial hypertension, and evidence of aortic aneurysm stood out as the greatest population attributable risk. But individuals with genetic connective tissue diseases like Marfan syndrome and those with bicuspid aortic valves carry the increased risk of aortic dissection at a younger age. Dissections involving the ascending aorta are of type A; if they involve only the descending aorta, they are of type B.

Fig.1 Transesophageal echocardiographic image of type A dissection. (Gawinecka, J., et al., 2017)

Pathogenesis of Acute Aortic Dissection

Aortic dissection occurs from a breach in the aortic intima, which results in the pulsatile flow contacting the medial layer. At the molecular level, aortic dissection is secondary to remodeling of the aortic architecture by inflammation and degradation of the extracellular matrix. Activated macrophages migrate into the tunica media and secrete matrix metalloproteinases (MMPs) and proinflammatory cytokines. The abnormal production of MMP-1, MMP-9, and MMP-12 causes the rapid destruction of collagen and elastin fibers.

Fig.2 Aortic dissection classification. (Tadros, R. O., et al., 2019)

Therapeutics Development for Acute Aortic Dissection

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

Protheragen delivers a one-stop solution for acute aortic dissection research, including advancing diagnostics development, pioneering biomarkers for early and accurate diagnosis of acute aortic dissection, and creating novel therapeutic strategies intended to bring new therapeutics to market to improve individual outcomes. Our personalized disease model creation services are available for strong preclinical research and also provide critical supporting work needed for successful drug development, such as in-depth pharmacokinetics and safety/effectiveness studies.

Therapeutic Development Services

Diverse Platforms

• Small Molecule Drug Development
• Gene Therapy Development
• Therapeutic Peptide Development

• Cell Therapy Development
• Therapeutic Antibody Development
• Therapeutic Protein Development

Animal Model Development for Acute Aortic Dissection

Animal models play an important role in elucidating pathophysiology, testing new therapies, and refining techniques. We know that each research is different, and we offer complete custom animal model development services to receive personalized solutions to their acute aortic dissection or any other cardiovascular disease studies.

Genetically Engineered Model

Various genetically modified models are developed to study specific genes or pathways involved in aortic wall integrity, inflammation, and remodeling, which can contribute to dissection.

• Fbn1^C1039G/+ model

• Other models

Surgical Animal Model

Surgical manipulation (e.g., partial ligation, direct injury) can be used to induce acute dissection, particularly for studying repair strategies.

• Endovascular procedure model

• Other models

Induced Animal Model

Experimental aortic dissection models are induced by dependent upon drug-mediated weakening of the aortic wall to induce dissection.

• β-aminopropionitrile-induced model
• Other models

• Angiotensin II (Ang II) infusion model

Protheragen is built on deep scientific knowledge, cutting-edge facilities, and a commitment to working with clients to accelerate open and collaborative innovation. Through the services we provide all in one place, we help our clients to confidently navigate the challenging environment of acute aortic dissection drug development to advance new, promising therapeutics more quickly. Contact us today and learn how our complete service can put your innovative therapeutic and other rare cardiovascular therapy breakthroughs in motion.

References

• Gawinecka, Joanna et al. "Acute aortic dissection: pathogenesis, risk factors and diagnosis." Swiss medical weekly 147 (2017): w14489.
• Tadros, Rami O et al. "Optimal Treatment of Uncomplicated Type B Aortic Dissection: JACC Review Topic of the Week." Journal of the American College of Cardiology 74.11 (2019): 1494-1504.