Cardiovascular Research Advance Access [Accepted Manuscript] published online on April 7, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp108
Induction of CRP3/MLP expression during vein arterialization is dependent on stretch rather than shear stress
Heart Institute (InCor), University of Sao Paulo Medical School
Corresponding authors: AAM (ayumi.miyakawa{at}incor.usp.br) & JEK (krieger{at}incor.usp.br) Laboratory of Genetic and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Eneas C. Aguiar, 44 – 10 andar, 05403-000 Sao Paulo – SP – Brazil, Tel.: 55 11 3069 5068, Fax: 55 11 3069 5022
Aims—: Cysteine- and glycine-rich protein 3/ muscle LIM-domain protein (CRP3/MLP) is a protein that mediates protein-protein interaction with actin filaments in the heart and is involved in muscle differentiation and vascular remodeling. Here, we assessed the induction of CRP3/MLP expression during arterialization in human and rat veins.
Methods and Results—: Vascular CRP3/MLP expression was mainly observed in arterial samples from both human and rat. Using quantitative real time RT-PCR, we demonstrated that CRP3/MLP expression was 10 times higher in smooth muscle cells (SMCs) from human mammary artery (h-MA) vs. saphenous vein (h-SV). In endothelial cells (ECs), CRP3/MLP was scarcely detected in either h-MA or h-SV. Using an ex vivo flow through system that mimics arterial condition, we observed induction of CRP3/MLP expression in arterialized h-SV. Interestingly, the upregulation of CRP3/MLP was primarily dependent on stretch stimulus in SMCs, rather than shear stress in ECs. Finally, using a rat vein in vivo arterialization model, early (1-14 days) CRP3/MLP immunostaining was observed predominantly in the inner layer and later (28-90 days) it appeared more scattered in the vessel layers.
Conclusion—: Here we provide evidence that CRP3/MLP is primarily expressed in arterial SMCs and that stretch is the main stimulus for CRP3/MLP induction in veins exposed to arterial hemodynamic conditions.
Time for primary review: 30 Days