DOI: 10.1161/circ.148.suppl_1.13461 ISSN: 0009-7322

Abstract 13461: Early Vascular Aging is Associated With Early Cardiac Aging, Upregulation of Left Ventricle Pro-Fibrotic and Inflammatory Genes and Memory Decline in Aged Dahl Salt-Sensitive Rats

Yulia N Grigorova, Ondrej Juhasz, Jeffrey M Long, Ross A McDevitt, Valentina I Zernetkina, Christopher H Morrell, Wen Wei, Peter R Rapp, Alexei Y Bagrov, Edward G Lakatta, Olga V Fedorova
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Introduction: Blood pressure (BP) begins to increase early in life in Dahl salt-sensitive rats (DSS) that consume a normal salt (NS) diet. Epidemiologic studies have shown that early vascular aging (EVA) is associated with central arterial stiffening (CAS) and hypertension, which develop earlier in life than expected in general population and contribute to cognitive impairment later in life.

Hypotheses: (i) DSS rats will develop EVA earlier in life on NS diet, and with advancing age will exhibit early CV aging; (ii) In DSS, CV remodeling and CAS are implicated in memory decline. We tested these hypotheses using a longitudinal repeated measure design in DSS and their parental breed Sprague-Dawley rats (SD) at 3- & 12-mo of age.

Methods: Male SD and DSS were kept on NS diet (0.5% NaCl; n=8/group) for entire experiment. Repeated measures of systolic BP (SBP), pulse wave velocity (PWV; an index of CAS), echocardiography, and non-repeated measures of Morris water maze (MWM) to test spatial memory, aortic collagen, elastin (histochemistry), and left ventricle (LV) mRNA expression (qPCR) were assessed at 3- & 12-mo. Data analyses: linear mixed-effect 2-way ANOVA, t-test & linear regression (LR) modeling. A 2-sided p<0.05 was considered significant.

Results: SBP, PWV, aortic weight, wall thickness and collagen/elastin ratio were higher in DSS-3 vs. SD-3, and in DSS-12 vs. DSS-3. RWT and LV expression of pro-fibrotic, inflammatory and senescence genes were higher in DSS-12 vs. DSS-3 and vs. SD-12 (Table). DSS-12 spent more time to find a hidden platform in MWM vs. SD-12; their impaired spatial hippocampal memory was positively associated with PWV and LV mass by LR analysis.

Conclusions: EVA, indexed as higher BP, PWV and aortic remodeling was associated with early CV aging, manifested by activation of LV senescence, inflammatory and pro-fibrotic genes and by higher rates of age-associated changes in BP, RWT and LV mass in DSS vs. SD. In DSS, early CV aging was associated with memory decline.

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