KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis (original) (raw)

• Saffitz, J.E. & Schwartz, C.J. Coronary atherosclerosis and thrombosis underlying acute myocardial infarction. Cardiol. Clin. 5, 21–30 (1987).
  Article CAS PubMed Google Scholar
• Libby, P. & Aikawa, M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat. Med. 8, 1257–1262 (2002).
  Article CAS PubMed Google Scholar
• Falk, E., Nakano, M., Benton, J.F., Finn, A.V. & Virmani, R. Update on acute coronary syndromes: the pathologists′ view. Eur. Heart J. 34, 719–728 (20123).
  Article PubMed CAS Google Scholar
• Falk, E., Shah, P.K. & Fuster, V. Coronary plaque disruption. Circulation 92, 657–671 (1995).
  Article CAS PubMed Google Scholar
• Virmani, R., Kolodgie, F.D., Burke, A.P., Farb, A. & Schwartz, S.M. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 20, 1262–1275 (2000).
  Article CAS PubMed Google Scholar
• Lee, R.T. & Libby, P. The unstable atheroma. Arterioscler. Thromb. Vasc. Biol. 17, 1859–1867 (1997).
  Article CAS PubMed Google Scholar
• Ross, R. Atherosclerosis–an inflammatory disease. N. Engl. J. Med. 340, 115–126 (1999).
  Article CAS PubMed Google Scholar
• Libby, P. Inflammation in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 32, 2045–2051 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Glass, C.K. & Witztum, J.L. Atherosclerosis: the road ahead. Cell 104, 503–516 (2001).
  Article CAS PubMed Google Scholar
• Libby, P., Ridker, P.M. & Hansson, G.K. Progress and challenges in translating the biology of atherosclerosis. Nature 473, 317–325 (2011).
  Article CAS PubMed Google Scholar
• Gomez, D. & Owens, G.K. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc. Res. 95, 156–164 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Rong, J.X., Shapiro, M., Trogan, E. & Fisher, E.A. Transdifferentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc. Natl. Acad. Sci. USA 100, 13531–13536 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Martin, K. et al. Thrombin stimulates smooth muscle cell differentiation from peripheral blood mononuclear cells via protease-activated receptor-1, RhoA, and myocardin. Circ. Res. 105, 214–218 (2009).
  Article CAS PubMed Google Scholar
• Caplice, N.M. et al. Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Proc. Natl. Acad. Sci. USA 100, 4754–4759 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Iwata, H. et al. Bone marrow-derived cells contribute to vascular inflammation but do not differentiate into smooth muscle cell lineages. Circulation 122, 2048–2057 (2010).
  Article CAS PubMed Google Scholar
• Wamhoff, B.R. et al. A G/C element mediates repression of the SM22α promoter within phenotypically modulated smooth muscle cells in experimental atherosclerosis. Circ. Res. 95, 981–988 (2004).
  Article CAS PubMed Google Scholar
• Feil, S. et al. Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis. Circ. Res. 115, 662–667 (2014).
  Article CAS PubMed Google Scholar
• Swirski, F.K. & Nahrendorf, M. Do vascular smooth muscle cells differentiate to macrophages in atherosclerotic lesions? Circ. Res. 115, 605–606 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Allahverdian, S., Chehroudi, A.C., McManus, B.M., Abraham, T. & Francis, G.A. Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis. Circulation 129, 1551–1559 (2014).
  Article CAS PubMed Google Scholar
• Cordes, K.R. et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460, 705–710 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Yoshida, T., Kaestner, K.H. & Owens, G.K. Conditional deletion of Krüppel-like factor 4 delays downregulation of smooth muscle cell differentiation markers but accelerates neointimal formation following vascular injury. Circ. Res. 102, 1548–1557 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Deaton, R.A., Gan, Q. & Owens, G.K. Sp1-dependent activation of KLF4 is required for PDGF-BB–induced phenotypic modulation of smooth muscle. Am. J. Physiol. Heart Circ. Physiol. 296, H1027–H1037 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Yoshida, T., Gan, Q. & Owens, G.K. Kruppel-like factor 4, Elk-1, and histone deacetylases cooperatively suppress smooth muscle cell differentiation markers in response to oxidized phospholipids. Am. J. Physiol. Cell Physiol. 295, C1175–C1182 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Thomas, J.A. et al. PDGF-DD, a novel mediator of smooth muscle cell phenotypic modulation, is upregulated in endothelial cells exposed to atherosclerosis-prone flow patterns. Am. J. Physiol. Heart Circ. Physiol. 296, H442–H452 (2009).
  Article CAS PubMed Google Scholar
• Pidkovka, N.A. et al. Oxidized phospholipids induce phenotypic switching of vascular smooth muscle cells in vivo and in vitro. Circ. Res. 101, 792–801 (2007).
  Article CAS PubMed Google Scholar
• Alexander, M.R. & Owens, G.K. Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu. Rev. Physiol. 74, 13–40 (2012).
  Article CAS PubMed Google Scholar
• Gomez, D., Shankman, L.S., Nguyen, A.T. & Owens, G.K. Detection of histone modifications at specific gene loci in single cells in histological sections. Nat. Methods 10, 171–177 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Klein, D., Benchellal, M., Kleff, V., Jakob, H.G. & Ergun, S. Hox genes are involved in vascular wall-resident multipotent stem cell differentiation into smooth muscle cells. Sci. Rep. 3, 2178 (2013).
  Article PubMed PubMed Central Google Scholar
• Klein, D. et al. Vascular wall-resident CD44+ multipotent stem cells give rise to pericytes and smooth muscle cells and contribute to new vessel maturation. PLoS ONE 6, e20540 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Xiao, Q. et al. Sca-1+ progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. Arterioscler. Thromb. Vasc. Biol. 26, 2244–2251 (2006).
  Article CAS PubMed Google Scholar
• Xiao, Q., Zeng, L., Zhang, Z., Hu, Y. & Xu, Q. Stem cell-derived Sca-1+ progenitors differentiate into smooth muscle cells, which is mediated by collagen IV-integrin α1/β1/αv and PDGF receptor pathways. Am. J. Physiol. Cell Physiol. 292, C342–C352 (2007).
  Article CAS PubMed Google Scholar
• Passman, J.N. et al. A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1+ smooth muscle progenitor cells. Proc. Natl. Acad. Sci. USA 105, 9349–9354 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• McDonald, O.G., Wamhoff, B.R., Hoofnagle, M.H. & Owens, G.K. Control of SRF binding to CArG box chromatin regulates smooth muscle gene expression in vivo. J. Clin. Invest. 116, 36–48 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Vladykovskaya, E. et al. Reductive metabolism increases the proinflammatory activity of aldehyde phospholipids. J. Lipid Res. 52, 2209–2225 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–872 (2007).
  Article CAS PubMed Google Scholar
• Cherepanova, O.A. et al. Oxidized phospholipids induce type VIII collagen expression and vascular smooth muscle cell migration. Circ. Res. 104, 609–618 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Salmon, M., Gomez, D., Greene, E., Shankman, L. & Owens, G.K. Cooperative binding of KLF4, pELK-1, and HDAC2 to a G/C repressor element in the SM22α promoter mediates transcriptional silencing during SMC phenotypic switching in vivo. Circ. Res. 111, 685–696 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Regan, C.P., Adam, P.J., Madsen, C.S. & Owens, G.K. Molecular mechanisms of decreased smooth muscle differentiation marker expression after vascular injury. J. Clin. Invest. 106, 1139–1147 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Feinberg, M.W. et al. The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. EMBO J. 26, 4138–4148 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Liao, X. et al. Kruppel-like factor 4 regulates macrophage polarization. J. Clin. Invest. 121, 2736–2749 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Sharma, N. et al. Myeloid Krüppel-like factor 4 deficiency augments atherogenesis in _Apoe_−/− mice–brief report. Arterioscler. Thromb. Vasc. Biol. 32, 2836–2838 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Zhou, G. et al. Endothelial Krüppel-like factor 4 protects against atherothrombosis in mice. J. Clin. Invest. 122, 4727–4731 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Nguyen, A.T. et al. Smooth muscle cell plasticity: fact or fiction? Circ. Res. 112, 17–22 (2013).
  Article CAS PubMed Google Scholar
• Tang, Z. et al. Differentiation of multipotent vascular stem cells contributes to vascular diseases. Nat. Commun. 3, 875 (2012).
  Article PubMed CAS Google Scholar
• Foster, K.W. et al. Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia. Oncogene 24, 1491–1500 (2005).
  Article CAS PubMed PubMed Central Google Scholar
• Jaubert, J., Cheng, J. & Segre, J.A. Ectopic expression of Krüppel-like factor 4 (Klf4) accelerates formation of the epidermal permeability barrier. Development 130, 2767–2777 (2003).
  Article CAS PubMed Google Scholar
• Katz, J.P. et al. The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon. Development 129, 2619–2628 (2002).
  Article CAS PubMed Google Scholar
• Katz, J.P. et al. Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Gastroenterology 128, 935–945 (2005).
  Article CAS PubMed Google Scholar
• Dandré, F. & Owens, G.K. Platelet-derived growth factor-BB and Ets-1 transcription factor negatively regulate transcription of multiple smooth muscle cell differentiation marker genes. Am. J. Physiol. Heart Circ. Physiol. 286, H2042–H2051 (2004).
  Article PubMed Google Scholar
• Clément, N. et al. Notch3 and IL-1β exert opposing effects on a vascular smooth muscle cell inflammatory pathway in which NF-κB drives crosstalk. J. Cell Sci. 120, 3352–3361 (2007).
  Article PubMed CAS Google Scholar
• Vengrenyuk, Y. et al. Cholesterol loading reprograms the microRNA-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype. Arterioscler. Thromb. Vasc. Biol. 35, 535–546 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Owens, G.K. Regulation of differentiation of vascular smooth muscle cells. Physiol. Rev. 75, 487–517 (1995).
  Article CAS PubMed Google Scholar
• Owens, G.K., Kumar, M.S. & Wamhoff, B.R. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol. Rev. 84, 767–801 (2004).
  Article CAS PubMed Google Scholar
• Wirth, A. et al. G12–G13-LARG–mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nat. Med. 14, 64–68 (2008).
  Article CAS PubMed Google Scholar
• Vooijs, M., Jonkers, J. & Berns, A. A highly efficient ligand-regulated Cre recombinase mouse line shows that loxP recombination is position dependent. EMBO Rep. 2, 292–297 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Alexander, M.R. et al. Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice. J. Clin. Invest. 122, 70–79 (2012).
  Article CAS PubMed Google Scholar
• McDonald, O.G. & Owens, G.K. Programming smooth muscle plasticity with chromatin dynamics. Circ. Res. 100, 1428–1441 (2007).
  Article CAS PubMed Google Scholar
• Langmead, B., Trapnell, C., Pop, M. & Salzberg, S.L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Zhang, Y. et al. Model-based analysis of ChIP-seq (MACS). Genome Biol. 9, R137 (2008).
  Article PubMed PubMed Central CAS Google Scholar
• Quinlan, A.R. & Hall, I.M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Mi, H., Muruganujan, A., Casagrande, J.T. & Thomas, P.D. Large-scale gene function analysis with the PANTHER classification system. Nat. Protoc. 8, 1551–1566 (2013).
  Article PubMed PubMed Central CAS Google Scholar
• Geisterfer, A.A., Peach, M.J. & Owens, G.K. Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ. Res. 62, 749–756 (1988).
  Article CAS PubMed Google Scholar