Aging and hypertension often go hand-in-hand, which makes it difficult to distinguish their biomechanical effects on arteries in clinical studies. While human aortic aging is characterized by reduced elastin (half-life∼70 years), mice age to a mere 2 years and most elastin remains intact. Knock-out of the elastin-associated glycoprotein fibulin-5 (Fbln5−/−) in mice yields a biomechanical phenotype that resembles human aging.
Design and method:
Adult male and female Fbln5+/+ and Fbln5−/− mice were studied under three conditions: untreated, after 14-day angiotensin-II infusion (AngII) at 490 ng/kg/min, or after 13 weeks on an 8%-NaCl chow with 3 g/L of L-NAME in the drinking water (L-NAME-NaCl). After tail-cuff blood pressure (BP) measurement and euthanasia, descending thoracic (DTA) and infrarenal abdominal (IAA) aortas were dissected and placed within a computer-controlled biaxial testing device. Pressure-diameter tests were performed at 95%, 100%, and 105% of the in vivo axial stretch and axial force-length tests at 10, 60, 100, and 140 mmHg. Data were fit using a nonlinear constitutive model.
Neither AngII nor L-NAME-NaCl changed wall thickness or axial stretch in the males (figure), hence circumferential stress and material stiffness increased due to BP elevation (e.g., significant in IAA, trend in DTA with AngII). This finding indicated a lack of adaptive remodeling. Stored strain energy was significantly lower in Fbln5−/− than Fbln5+/+ mice, but was not significantly influenced by AngII or L-NAME-NaCl. Pulse wave velocity, a measure of structural stiffness, increased due to AngII and L-NAME-NaCl in several groups, which was also BP-mediated. Females showed similar trends as males (not shown), except for strain energy, which increased with AngII independent of BP.
The present findings for AngII infusion were similar to prior results for the IAA, but very different for the DTA when compared to the 2.62-fold increase in wall thickness and significant decrease in axial stretch in wildtype mice. The prior dramatic changes depended in large part on inflammation. We suspect that the modest arterial remodeling observed herein in response to induced hypertension may have been due more to the genetic background strain of our mice (C57BL/6x129SvEv) than fibulin-5 deficiency.