細(xì)胞凋亡除了在發(fā)育和體內(nèi)平衡是具有重要性之外,，它還牽涉到許多疾病,，其中包括動脈粥樣硬化。 凋亡的內(nèi)皮細(xì)胞,，在粥樣硬化板塊處的,，會將被稱作凋亡小體的微泡釋放到循環(huán)之中，而其量的豐富程度與疾病的負(fù)指征相關(guān),。
在2009年12月8日的期刊中,，Zernecke 等人研究發(fā)現(xiàn),，來自內(nèi)皮細(xì)胞的凋亡小體中含有微RNA-126（miR-126），它們會被鄰近的血管細(xì)胞攝取,。 MiR-26增加了來自趨化因子受體CXCR4的信號,，而這又觸發(fā)了自動調(diào)節(jié)反饋環(huán)路，從而導(dǎo)致了CXCL12產(chǎn)生的增加,。CXCL12是CXCR4的配基,。 CXCL12可限制動脈粥樣硬化，而從動脈粥樣硬化病人身上分離出的凋亡小體可縮小不同的小鼠動脈粥樣硬化模型的粥樣斑塊的大小,。 因此,，垂死的內(nèi)皮細(xì)胞會以包裹的微RNA形式向鄰近的細(xì)胞發(fā)出警示信號以觸發(fā)一個能減少動脈粥樣硬化的復(fù)原反應(yīng)。（生物谷Bioon.com）
生物谷推薦原始出處：
Sci. Signal. , 8 December 2009 DOI: 10.1126/scisignal.2000610
Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection
Alma Zernecke1,2*, Kiril Bidzhekov1*, Heidi Noels1*, Erdenechimeg Shagdarsuren1, Lin Gan3, Bernd Denecke3, Mihail Hristov1, Thomas K?ppel4, Maliheh Nazari Jahantigh1, Esther Lutgens1,5, Shusheng Wang6, Eric N. Olson6, Andreas Schober1, and Christian Weber1,5
1 Institute of Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany.
2 Rudolf-Virchow-Center–DFG Research Center for Experimental Biomedicine, University of Würzburg, 97080 Würzburg, Germany.
3 Interdisciplinary Centre for Clinical Research BIOMAT, Department of Vascular Surgery, RWTH Aachen University, 52074 Aachen, Germany.
4 Department of Vascular Surgery, RWTH Aachen University, 52074 Aachen, Germany.
5 Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, 6200 MD Maastricht, the Netherlands.
6 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390–9148, USA.
Apoptosis is a pivotal process in embryogenesis and postnatal cell homeostasis and involves the shedding of membranous microvesicles termed apoptotic bodies. In response to tissue damage, the CXC chemokine CXCL12 and its receptor CXCR4 counteract apoptosis and recruit progenitor cells. Here, we show that endothelial cell–derived apoptotic bodies are generated during atherosclerosis and convey paracrine alarm signals to recipient vascular cells that trigger the production of CXCL12. CXCL12 production was mediated by microRNA-126 (miR-126), which was enriched in apoptotic bodies and repressed the function of regulator of G protein (heterotrimeric guanosine triphosphate–binding protein) signaling 16, an inhibitor of G protein–coupled receptor (GPCR) signaling. This enabled CXCR4, a GPCR, to trigger an autoregulatory feedback loop that increased the production of CXCL12. Administration of apoptotic bodies or miR-126 limited atherosclerosis, promoted the incorporation of Sca-1+ progenitor cells, and conferred features of plaque stability on different mouse models of atherosclerosis. This study highlights functions of microRNAs in health and disease that may extend to the recruitment of progenitor cells during other forms of tissue repair or homeostasis.
