Advertisement

Citations to this article

Abstract

The cyclin-dependent kinase inhibitors are key regulators of cell cycle progression. Although implicated in carcinogenesis, they inhibit the proliferation of a variety of normal cell types, and their role in diverse human diseases is not fully understood. Here, we report that p27Kip1 plays a major role in cardiovascular disease through its effects on the proliferation of bone marrow–derived (BM-derived) immune cells that migrate into vascular lesions. Lesion formation after mechanical arterial injury was markedly increased in mice with homozygous deletion of p27Kip1, characterized by prominent vascular infiltration by immune and inflammatory cells. Vascular occlusion was substantially increased when BM-derived cells from p27–/– mice repopulated vascular lesions induced by mechanical injury in p27+/+ recipients, in contrast to p27+/+ BM donors. To determine the contribution of immune cells to vascular injury, transplantation was performed with BM derived from RAG–/– and RAG+/+ mice. RAG+/+ BM markedly exacerbated vascular proliferative lesions compared with what was found in RAG–/– donors. Taken together, these findings suggest that vascular repair and regeneration is regulated by the proliferation of BM-derived hematopoietic and nonhematopoietic cells through a p27Kip1-dependent mechanism and that immune cells largely mediate these effects.

Authors

Manfred Boehm ... Xuan Qu, Elizabeth G. Nabel

×

Total citations by year

Year: 2014 2012 2010 2008 2006 2005 2004 Total
Citations: 3 1 4 3 4 2 2 19
Citation information

Citations to this article (19)

Title and authors Publication Year
Targeting PI3Kγ activity decreases vascular trauma-induced intimal hyperplasia through modulation of the Th1 response
NF Smirnova, S Gayral, C Pedros, G Loirand, N Vaillant, N Malet, S Kassem, D Calise, D Goudounèche, MP Wymann, E Hirsch, AP Gadeau, LO Martinez, A Saoudi, M Laffargue
Journal of Experimental Medicine 2014
A selective microRNA-based strategy inhibits restenosis while preserving endothelial function
G Santulli, A Wronska, K Uryu, TG Diacovo, M Gao, SO Marx, J Kitajewski, JM Chilton, KM Akat, T Tuschl, AR Marks, H Totary-Jain
Journal of Clinical Investigation 2014
TGF-  Signaling Mediates Endothelial-to-Mesenchymal Transition (EndMT) During Vein Graft Remodeling
BC Cooley, J Nevado, J Mellad, D Yang, CS Hilaire, A Negro, F Fang, G Chen, H San, AD Walts, RL Schwartzbeck, B Taylor, JD Lanzer, A Wragg, A Elagha, LE Beltran, C Berry, R Feil, R Virmani, E Ladich, JC Kovacic, M Boehm
Science Translational Medicine 2014
Magnolol attenuates neointima formation by inducing cell cycle arrest via inhibition of ERK1/2 and NF-κB activation in vascular smooth muscle cells
R Karki, OM Ho, DW Kim
Biochimica et Biophysica Acta (BBA) - General Subjects 2012
Deficiency of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 accelerates atherogenesis in apolipoprotein E-deficient mice
LM Akyürek, M Boehm, M Olive, AX Zhou, H San, EG Nabel
Biochemical and Biophysical Research Communications 2010
Perivascular T-Cell Infiltration Leads to Sustained Pulmonary Artery Remodeling after Endothelial Cell Damage
MJ Cuttica, T Langenickel, A Noguchi, RF Machado, MT Gladwin, M Boehm
American journal of respiratory cell and molecular biology 2010
Stat3-dependent acute Rantes production in vascular smooth muscle cells modulates inflammation following arterial injury in mice
JC Kovacic, R Gupta, AC Lee, M Ma, F Fang, CN Tolbert, AD Walts, LE Beltran, H San, G Chen, CS Hilaire, M Boehm
Journal of Clinical Investigation 2010
p27kip1 controls cell morphology and motility by regulating microtubule-dependent lipid raft recycling
B Belletti, I Pellizzari, S Berton, L Fabris, K Wolf, F Lovat, M Schiappacassi, S D'Andrea, MS Nicoloso, S Lovisa, M Sonego, P Defilippi, A Vecchione, A Colombatti, P Friedl, G Baldassarre
Molecular and cellular biology 2010
KIS protects against adverse vascular remodeling by opposing stathmin-mediated VSMC migration in mice
TH Langenickel, M Olive, M Boehm, H San, MF Crook, EG Nabel
Journal of Clinical Investigation 2008
p21Cip1 modulates arterial wound repair through the stromal cell–derived factor-1/CXCR4 axis in mice
M Olive, JA Mellad, LE Beltran, M Ma, T Cimato, AC Noguchi, H San, R Childs, JC Kovacic, M Boehm
Journal of Clinical Investigation 2008
Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction
HV Huikuri, K Kervinen, M Niemela, K Ylitalo, M Saily, P Koistinen, ER Savolainen, H Ukkonen, M Pietila, JK Airaksinen, J Knuuti, TH Makikallio
European Heart Journal 2008
Coronary artery restenosis: vascular biology and emerging therapeutic strategies
K Sarkar, SK Sharma, R Sachdeva, F Romeo, L Garza, JL Mehta
Expert Review of Cardiovascular Therapy 2006
Atheroma development in apolipoprotein E-null mice is not regulated by phosphorylation of p27Kip1 on threonine 187
SM Sanz-González, RM de Mera, NP Malek, V Andrés
Journal of Cellular Biochemistry 2006
Enzyme Inhibitors Series
M Boehm, M Crook
Enzyme Inhibitors Series 2006
Cytostatic gene therapy for occlusive vascular disease
JM González, V Andrés
Expert Opinion on Therapeutic Patents 2006
PPARα inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16INK4a
F Gizard, C Amant, O Barbier, S Bellosta, R Robillard, F Percevault, H Sevestre, P Krimpenfort, A Corsini, J Rochette, C Glineur, JC Fruchart, G Torpier, B Staels
Journal of Clinical Investigation 2005
p27kip1 Deficiency Confers Susceptibility to Gastric Carcinogenesis in Helicobacter pylori–Infected Mice
N Kuzushita, AB Rogers, NA Monti, MT Whary, MJ Park, BI Aswad, H Shirin, A Koff, H Eguchi, SF Moss
Gastroenterology 2005
The link between IFN-γ and allograft arteriopathy: is the answer NO?
RN Mitchell, AH Lichtman
Journal of Clinical Investigation 2004
Rationale and study design of the CardioGene Study: genomics of in-stent restenosis
SK Ganesh, KA Skelding, L Mehta, K O’Neill, J Joo, G Zheng, J Goldstein, R Simari, E Billings, NL Geller, D Holmes, WW O’Neill, EG Nabel
Pharmacogenomics 2004

Advertisement
Advertisement