Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice

Joshua E. Basford, Sheryl Koch, Ahmad Anjak, Vivek P. Singh, Eric G. Krause, Nathan Robbins, Neal Lee Weintraub, David Y. Hui, Jack Rubinstein

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Valvular disease is common in patients with Marfan syndrome and can lead to cardiomyopathy. However, some patients develop cardiomyopathy in the absence of hemodynamically significant valve dysfunction, suggesting alternative mechanisms of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1) in smooth muscle cells has been shown to cause vascular pathologies similar to Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and aortic aneurysms. This study used echocardiography and blood pressure monitoring in mouse models to determine whether inactivation of Lrp1 in vascular smooth muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence of valvular disease. Hemodynamic changes during treatment with captopril were also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice and progressed as they aged, whereas no significant aortic dilation was detected in wild type littermates. Diastolic blood pressure was lower and pulse pressure higher in Lrp1-knockout mice, which was normalized by treatment with captopril. Aortic dilation was followed by development of aortic insufficiency and subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle cell Lrp1 deficiency results in aortic dilation and insufficiency that causes secondary cardiomyopathy that can be improved by captopril. These findings provide novel insights into mechanisms of cardiomyopathy associated with vascular activation and offer a new model of valvular cardiomyopathy.

Original languageEnglish (US)
Article numbere82026
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 29 2013

Fingerprint

Low Density Lipoprotein Receptor-Related Protein-1
cardiomyopathy
Cardiomyopathies
blood vessels
smooth muscle
Smooth Muscle
Blood Vessels
Muscle
Captopril
receptors
Dilatation
mice
Blood Pressure
Smooth Muscle Myocytes
Blood pressure
Cells
Marfan Syndrome
myocytes
proteins
Knockout Mice

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Basford, J. E., Koch, S., Anjak, A., Singh, V. P., Krause, E. G., Robbins, N., ... Rubinstein, J. (2013). Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice. PloS one, 8(11), [e82026]. https://doi.org/10.1371/journal.pone.0082026

Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice. / Basford, Joshua E.; Koch, Sheryl; Anjak, Ahmad; Singh, Vivek P.; Krause, Eric G.; Robbins, Nathan; Weintraub, Neal Lee; Hui, David Y.; Rubinstein, Jack.

In: PloS one, Vol. 8, No. 11, e82026, 29.11.2013.

Research output: Contribution to journalArticle

Basford, Joshua E. ; Koch, Sheryl ; Anjak, Ahmad ; Singh, Vivek P. ; Krause, Eric G. ; Robbins, Nathan ; Weintraub, Neal Lee ; Hui, David Y. ; Rubinstein, Jack. / Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice. In: PloS one. 2013 ; Vol. 8, No. 11.
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