Bone marrow deficiency of TRPC3 channel reduces early lesion burden and necrotic core of advanced plaques in a mouse model of atherosclerosis.

Abstract

AIMS:

Macrophage apoptosis plays a determinant role in progression of atherosclerotic lesions. An important goal in atherosclerosis research is to identify new components of macrophage apoptosis that can eventually be exploited as molecular targets in strategies aimed at manipulating macrophage function in the lesion. In the previous work from our laboratory, we have shown that transient receptor potential canonical 3 (TRPC3) channel is an obligatory component of survival mechanisms in human and murine macrophages and that TRPC3-deficient non-polarized bone marrow-derived macrophages exhibit increased apoptosis, suggesting that in vivo TRPC3 might influence lesion development. In the present work, we used a bone marrow transplantation strategy as a first approach to examine the impact of macrophage deficiency of TRPC3 on early and advanced atherosclerotic lesions of Apoe(-/-) mice.

METHODS AND RESULTS:

After 3 weeks of high-fat diet, lesions in mice transplanted with bone marrow from Trpc3(-/-) donors were smaller and with reduced cellularity than controls. Advanced lesions from these mice exhibited reduced necrotic core, less apoptotic macrophages, and increased collagen content and cap thickness. In vitro, TRPC3-deficient macrophages polarized to the M1 phenotype showed reduced apoptosis, whereas both M1 and M2 macrophages had increased efferocytic capacity.

CONCLUSIONS:

Bone marrow deficiency of TRPC3 has a dual beneficial effect on lesion progression by reducing cellularity at early stages and necrosis in the advanced plaques. Our findings represent the first evidence for a role of a member of the TRPC family of cation channels in mechanisms associated with atherosclerosis.

• Authors: Jean-Yves Tano, Sumeet Solanki, Robert H Lee, Kathryn Smedlund, Lutz Birnbaumer, Guillermo Vazquez
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 101 Issue 1 Pg. 138-44 (Jan 01 2014) ISSN: 1755-3245 [Electronic] England
• PMID: 24101197 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• TRPC Cation Channels
• TRPC3 cation channel

Topics

• Animals
• Aorta (pathology)
• Apoptosis
• Atherosclerosis (etiology, metabolism, pathology)
• Bone Marrow (metabolism)
• Disease Models, Animal
• Female
• Macrophages (pathology)
• Mice
• Necrosis
• TRPC Cation Channels (metabolism)