Differential hypertensive protease expression in the thoracic versus abdominal aorta

Area of Science:

• Cardiovascular Biology
• Protease Systems
• Vascular Remodeling

Background:

• Hypertension (HTN) is a major risk factor for cardiovascular disease, contributing to pathological remodeling of the aorta.
• Regional differences in aortic pathology suggest distinct protease system activities in the thoracic aorta (TA) and abdominal aorta (AA).

Purpose of the Study:

• To test the hypothesis that matrix metalloproteinases (MMPs) and cathepsins expression in the TA and AA are differentially affected by HTN.
• To investigate Angiotensin II (AngII)-dependent and pressure-dependent alterations in aortic protease systems.

Main Methods:

• Induction of HTN in mice using AngII infusion and comparison with spontaneously hypertensive mice.
• Quantification of MMPs (MMP-2, MMP-9) and cathepsins (S, K, L) gene expression and protein levels in TA and AA via real-time PCR and immunoblotting/zymography.
• Monitoring of blood pressure using CODA tail cuff plethysmography.

Main Results:

• AngII-induced HTN increased systolic blood pressure and MMP-2 gene expression in the TA.
• Tissue inhibitor of metalloproteinases-1 increased in the TA, while tissue inhibitor of metalloproteinases-2 decreased in the AA of hypertensive mice.
• Cathepsin K elevated in the TA, while cathepsin L and cystatin C were inhibited in the AA of hypertensive groups.

Conclusions:

• HTN induces regional alterations in aortic gene expression of MMPs and cathepsins.
• These findings highlight AngII-dependent and pressure-dependent effects, contributing to differential remodeling in the TA and AA.
• Further research may identify targeted therapies for aortic pathology based on regional heterogeneity.