Differential Hypertensive Protease Expression in the Thoracic Versus Abdominal Aorta

Abstract

Background-Hypertension (HTN), which is a major risk factor for cardiovascular morbidity and mortality, can drive pathologic remodeling of the macro-and microcirculation. Patterns of aortic pathology differ, however, suggesting regional heterogeneity of the pressure-sensitive protease systems triggering extracellular matrix remodeling in the thoracic (TA) and abdominal aortas (AA). This study tested the hypothesis that the expression of two major protease systems (matrix metalloproteinases [MMPs] and cathepsins) in the TA and AA would be differentially affected with HTN.Methods-Normotensive (BPN3) mice at 14-16 weeks of age underwent implantation of osmotic infusion pumps for 28-day angiotensin II (AngII) delivery (1.46 mg/kg/day; BPN3+AngII; n = 8) to induce HTN. The TA and AA were harvested to determine levels of MMP-2, MMP-9, and membrane type 1-MMP, and cathepsins S, K, and L were evaluated in agematched BPN3 (n = 8) control and BPH2 spontaneously hypertensive mice (non-AngII pathway; n = 7). Blood pressure was monitored via CODA tail cuff plethysmography (Kent Scientific Corporation, Torrington, Conn). Quantitative real-time polymerase chain reaction and Full anesthesia was initiated for the terminal study, and the TA and AA were harvested by posterolateral thoracotomy and laparotomy, respectively. Tissue harvest included the descending TA from the crossing azygous vein to the diaphragmatic hiatus and the AA from Ruddy et al. Regional mechanosensitive signalingThoracic aortic remodeling involves restructuring of the ECM through the activity of several proteases. The MMP-2 and MT1-MMP transcriptional activity observed in this study is contradictory to that previously described for an ex vivo method of tension application. 6,29 Specifically, there was an unexpected decrease in expression of MMP-2 and a lack of Ruddy et al.