DAB2IP: unifying cardiovascular pathogenesis and cardiovascular brain crosstalk

Area of Science:

• Molecular Biology
• Cardiovascular Biology
• Neurobiology

Background:

• Cardiovascular diseases (CVDs) and brain disorders are significant global health burdens with linked pathologies.
• The DAB2IP gene, known as a tumor suppressor, plays a crucial role in both cardiovascular and neurological functions.
• Understanding the dual role of DAB2IP is key to addressing comorbid cardiovascular and brain conditions.

Purpose of the Study:

• To elucidate the multifaceted roles of the DAB2IP gene in cardiovascular and neurological systems.
• To explore DAB2IP's involvement in the pathogenesis of atherosclerosis and its genetic associations with cardiovascular diseases.
• To investigate DAB2IP's function in the cardiovascular-brain circuit, including neuron migration and blood-brain barrier integrity.

Main Methods:

• Review of DAB2IP's functions in endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and neuronal pathways.
• Analysis of DAB2IP's genetic associations with coronary artery disease (CAD), aortic aneurysm (AA), and aortic dissection (AD).
• Examination of DAB2IP's role in blood-brain barrier (BBB) integrity and immune-neural remodeling.

Main Results:

• DAB2IP suppresses inflammation and apoptosis in ECs via TNF signaling.
• DAB2IP inhibits VSMC phenotypic switching through JAK-STAT and PI3K-Akt pathways.
• DAB2IP regulates neuron migration, BBB integrity in Alzheimer's models, and arterial immune-neural remodeling.

Conclusions:

• DAB2IP is a critical regulator in both cardiovascular and neurological systems, linking these pathologies.
• Emerging DAB2IP-targeted therapies, including epigenetic modulators and exosomal circRNA delivery, show preclinical promise.
• Further validation is needed to assess the long-term safety and efficacy of DAB2IP-targeted strategies in diverse models.