Abstract P112: Decreased α-Myosin Expression is Associated with Left Ventricular Hypertrophy in Hypertensive Caribbean Vervets

Abstract

Caribbean vervets ( Chlorocebus aethiops sabeus ) develop hypertension (HT; Systolic Blood Pressure ≥ 140 mmHg) in over 30% (125/345) of the outbred population. Elevated total peripheral resistance in HT increases cardiac afterload, which may lead to left ventricular hypertrophy (LVH) and cardiac remodeling. We hypothesize that prolonged spontaneous HT is associated with LVH, cardiac and aortic fibrosis, as well as differential transcription of myocardial contractile proteins. Vervets were characterized as HT (SBP = 170 ± 25.3 mmHg; n=125) or normotensive (NT, SBP = 99 ± 14.5 mmHg; n=148) using forearm plethysmography (ketamine sedated;15 mg/kg i.m.). Cardiomyocyte cross-sectional area was greater in HT compared to NT animals (HT 283 ± 52 μm 2 , n=9 vs NT 114 ± 8 μm 2 , n=10; p<0.01). Average collagen stained as a function of tissue area was similar in left ventricular myocardium of HT and NT animals (HT 14.17 ± 3.13% or 0.17/1.21 mm 2 , n=9 vs NT 12.22 ± 0.80% or 0.16/1.27 mm 2 , n=10; p>0.05). Aortic adventia collagen area was greater in HT compared to NT vervets (HT 66.12 ± 4.22% or 0.60/0.90 mm 2 , n=6 vs NT 54.53 ± 2.21% or 0.56/1.02 mm 2 , n=10; p<0.05). Total tissue collagen was estimated using a hydroxyproline assay. Collagen content was not different between HT and NT vervets for left ventricular myocardium (HT 194.02 ± 8.61 μg/mL, n=11 vs NT 201.70 ± 18.89 μg/mL, n=10; p=0.71) or aorta (HT 745.64 ± 44.49 μg/mL, n=11 vs NT 668.39 ± 31.06 μg/mL, n=11; p=0.17). Myosin gene expression (α and β) was estimated using RT-PCR of mRNA in left ventricular myocardium of NT (SBP = 98.91 ±10.89 mmHg; n=20) and HT (SBP = 171.51 ± 30.28 mmHg; n=17) vervets. α-myosin was downregulated in HT compared to NT vervets (HT RQ = 0.10 ± 0.03 vs. NT RQ = 0.22 ± 0.04; p<0.05), while β-myosin expression was not different (HT RQ = 0.22 ± 0.17 vs. NT RQ = 0.20 ± 0.16; p=0.83). Thus, spontaneous HT in outbred vervets induces LVH in response to factors other than cardiac fibrosis. Myosin gene expression may shift from α-myosin to other contractile protein isoforms, characteristic of human heart failure. In this nonhuman primate model, HT does not induce significant aortic fibrosis that may occur in aged animals. Future studies will further characterize contractile and pro-inflammatory proteins in LVH of spontaneous HT vervets.