Ascending Aortic Aneurysm

An ascending thoracic aortic aneurysm is a focal dilatation of the proximal portion of the aorta. If neglected, an ascending thoracic aortic aneurysm can cause serious complications, including aortic dissection and rupture, and carries a mortality of 50% within 24 hours. Protheragen is your research services provider for end-to-end drug development of rare cardiovascular diseases, particularly complex diseases like ascending thoracic aortic aneurysm. With diagnostics, therapeutics, and disease model development all in one place, our integrated solution enables researchers and biopharma partners to make breakthrough discoveries faster.

Introduction to Ascending Aortic Aneurysm

Ascending aorta dilatation is very indolent as it is a silent process that takes several years and has an early asymptomatic stage. Complications consist of aortic dissection or rupture, pericardial bleeding, cardiac tamponade, and occlusions of the aorta. Ascending aortic aneurysm, an important cause of adult death, is not well investigated compared to the abdominal aneurysm. The annual estimated incidence of ascending thoracic aortic aneurysm is between 5 and 10 per 100,000 people, and there is an upward trend at present.

Fig.1 Summary of potential mechanosensitive pathways in vascular health and disease in ascending thoracic aortic aneurysms. (Ganizada, B. H., et al., 2024)

Pathogenesis of Ascending Aortic Aneurysm

Increasing evidence of heterogeneity of etiology of thoracic aortic aneurysms comes from studies of genetic aneurysm (ascending aortic aneurysm) and environmentally mediated risk factors (descending aortic aneurysm). Some genes have been firmly associated as being related to heritable ascending thoracic aortic aneurysms, with a given protein encoding a contraction and adhesion characteristic of VSMCs to ECM. They also participate in the TGF-β signaling and VSMC metabolism.

Fig.2 Summary of common risks in ascending thoracic aortic aneurysms. (Ganizada, B. H., et al., 2024)

Therapeutics Development for Ascending Aortic Aneurysm

The management of the ascending aortic aneurysm is in continuous evolution, although, at the moment, the gold standard for therapy of larger aneurysms is surgery. Interest in new drugs that may arrest aneurysm enlargement and rupture is in development.

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

What sets us apart is that we have a deep specialization in rare disease and our capability to close the gap between concept and practical application. In diagnostics, we combine advanced biomarker discovery and other technologies aimed at enabling the precise detection of diseases. For therapeutics, we create customized drug discovery programs, from target validation to preclinical optimization, focused on mechanisms capable of addressing the distinct pathophysiology of rare cardiovascular diseases. We also establish strong disease models in vitro and in vivo that reflect human disease to support testing efficacy and safety, and offer extensive preclinical research support, such as pharmacokinetics studies and safety testing.

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 Ascending Aortic Aneurysm

Animal models are invaluable in the investigation of the pathogenesis and the testing of new diagnostic and therapeutic approaches for ascending aortic aneurysm. We are dedicated to providing a complete, one-stop service for the development of animal models to help you move your research forward at speed and to produce scientifically robust, high-quality data.

Genetically Engineered Model

By introducing specific gene mutations or alterations that mimic human genetic predispositions, construct animal models of ascending aortic aneurysm.

• fibulin-4-deficient model
• Other models

• Tgfbr2 mutation model

Surgical Animal Model

These models involve direct surgical manipulation of the aorta to initiate aneurysm formation, often by inducing injury or altering blood flow.

• Cover-then-cut method
• Other models

• Ascending aortic constriction

Induced Animal Model

These models typically rely on administering specific compounds that induce changes in the aortic wall, leading to aneurysm formation.

• Elastase-induced model
• Other models

• Angiotensin II-infused ApoE^-/- model

Protheragen's interdisciplinary team of researchers have the experience of decades of cardiovascular biology combined with the latest technologies. By providing holistic solutions of diagnostics and therapeutics development, we help streamline timelines, remaining in compliance with worldwide regulatory standards, and our flexible service models guarantee the ability to scale to best fit a client's requirements. Get in touch today to see how we can advance your next breakthrough.

Reference

• Ganizada, Berta H et al. "Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections." Basic research in cardiology 119.3 (2024): 371-395.