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Left Ventricular Hypertrophy Is Associated With Decreased α But Not β‐Myosin Gene Expression in Spontaneously Hypertensive Nonhuman Primates
Author(s) -
Weaver Chelsea Christina,
Gutierrez Anthony,
Osborn Jeffrey L
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1206.7
Subject(s) - medicine , muscle hypertrophy , blood pressure , left ventricular hypertrophy , cardiology , endocrinology , myosin , essential hypertension , biology , biophysics
Essential hypertension (EH) is associated with increased risk of cardiovascular disease and heart failure. Left ventricular hypertrophy (LVH) also increases the risk of heart failure yet the mechanisms underlying ventricular cardiac remodeling remain unclear. The vervet monkey ( Chlorocebus aethiops sabaeus ) is a highly translational model of hypertension as they share more than 97% of their genome with humans and naturally develop spontaneous hypertension. We have identified vervets from outbred colonies as either hypertensive (HT, systolic blood pressure, SBP≥140 mmHg) or normotensive (NT, SBP<120 mmHg) using forearm plethysmography under ketamine sedation (15 mg/kg i.m.). We hypothesize that in the vervet, spontaneous hypertension is associated with LVH combined with altered gene expression of myocardial contractile proteins and pro‐inflammatory agents similar to other dietary, surgical pathology or pharmacological induced models of hypertension in quadripedal mammals. Cardiomyocyte cross‐sectional area of left but not right ventricles was greater in HT than NT individuals (HT 1658μm 2 ±515, n=6 vs. NT 791μm 2 ±210, n=7; p<0.01) demonstrating significant morphological LVH in this model of spontaneous hypertension. Semi‐quantitative RT‐PCR assessed left ventricular α/β myosin gene expression of HT (mean SBP=171.5±7.3 mmHg; n=15) and NT (mean SBP 98.9±2.4 mmHg; n=14) vervets. Gene expression in left ventricular myocardium was normalized using reference gene RPS13A. α‐myosin was downregulated in HT versus NT vervets (HT RQ=0.10±0.03 vs. NT RQ=0.22±0.04; p<0.05), whereas β‐myosin expression was not different (HT RQ=0.22±0.17 vs. NT RQ=0.20±0.16; p=0.83). The LVH pro‐inflammatory intracellular adhesion molecule 1 (ICAM‐1) gene expression also was measured using RNA extracted from left ventricular myocardium. ICAM‐1 gene expression in HT and NT vervets was not different (HT RQ=0.11±0.03 vs. NT 0.15±0.07; p=0.47). We conclude that downregulation of α‐myosin in the left ventricular myocardium in HT vervets may represent the early onset stages of the shift of α to β myosin characteristic of long‐term LVH and established heart failure after chronic elevation of systemic vascular resistance and blood pressure. At present, pro‐inflammatory ICAM‐1 is not associated with development of LVH in HT vervets. Future studies will further divide nonhuman primate groups into HT with LVH, HT without LVH, and NT to more selectively evaluate molecular protein expression with myocardial hypertrophy in spontaneous hypertension as well as the expression of additional inflammatory cytokines within the myocardium. Support or Funding Information Supported by Biomedical Sciences Research Group, L.L.C.