Neointimal hyperplasia and vasoreactivity are controlled by genetic elements on rat chromosome 3

Andrea L.Nestor Kalinoski, Ramona S. Ramdath, Kay M. Langenderfer, Saad Sikanderkhel, Sarah DeRaedt, Marlene Welch, James L. Park, Timothy Pringle, Bina Joe, George T. Cicila, David C. Allison

Research output: Contribution to journalArticlepeer-review

Abstract

Neointimal hyperplasia (NIH) can lead to restenosis after clinical vascular interventions. NIH results from complex and poorly understood interactions between signaling cascades in the extracellular matrix and the disrupted endothelium, which lead to vessel occlusion. Quantitative trait loci (QTLs) were reported previously on rat chromosomes 3 and 6 through linkage analysis of postinjury NIH in midiliac arterial sections. In the current study, substitution mapping validated the RNO3 NIH QTL but not the RNO6 NIH QTL. The SHR.BN3 congenic strain had a 3-fold increase in the percentage of NIH compared with the parental spontaneously hypertensive rat strain. A double congenic study of RNO3RNO6 NIH QTL segments suggested less than additive effects of these 2 genomic regions. To test the hypothesis that changes in vessel dynamics account for the differences in NIH formation, we performed vascular reactivity studies in the Brown Norway (BN), spontaneously hypertensive rat (SHR), SHR.BN3, and SHR.BN6 strains. De-endothelialized left common carotid artery rings of the SHR.BN3 showed an increased vascular responsiveness when treated with serotonin or prostaglandin F2α, with significant differences in EC50 and maximum effect (P<0.01) values compared with the spontaneously hypertensive rat parental strain. Because both vascular reactivity and percentage of NIH formation in the SHR.BN3 strain are significantly higher than the SHR strain, we postulate that these traits may be associated and are controlled by genetic elements on RNO3. In summary, these results confirm that the RNO3 NIH QTL carries the gene(s) contributing to postinjury NIH formation.

Original languageEnglish (US)
Pages (from-to)555-561
Number of pages7
JournalHypertension
Volume55
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Congenics
  • Neointimal hyperplasia
  • QTL
  • Rat
  • Vascular reactivity

ASJC Scopus subject areas

  • Internal Medicine

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