Endothelial progenitor cells in the host defense response
Extensive injury of endothelial cells in blood vasculature, especially in the microcirculatory system, frequently occurs in hosts suffering from sepsis and the accompanied systemic inflammation. Pathological factors, including toxic components derived from invading microbes, oxidative stress associated with tissue ischemia/reperfusion, and vessel active mediators generated during the inflammatory response, are known to play important roles in mediating endothelial injury. Collapse of microcirculation and tissue edema developed from the failure of endothelial barrier function in vital organ systems, including the lung, brain, and kidney, are detrimental, which often predict fatal outcomes. The host body possesses a substantial capacity for maintaining vascular homeostasis and repairing endothelial damage. Bone marrow and vascular wall niches house endothelial progenitor cells (EPCs). In response to septic challenges, EPCs in their niche environment are rapidly activated for proliferation and angiogenic differentiation. In the meantime, release of EPCs from their niches into the blood stream and homing of these vascular precursors to tissue sites of injury are markedly increased. The recruited EPCs actively participate in host defense against endothelial injury and repair of damage in blood vasculature via direct differentiation into endothelial cells for re-endothelialization as well as production of vessel active mediators to exert paracrine and autocrine effects on angiogenesis/vasculogenesis. In recent years, investigations on significance of EPCs in host defense and molecular signaling mechanisms underlying regulation of the EPC response have achieved substantial progress, which promotes exploration of vascular precursor cell-based approaches for effective prevention and treatment of sepsis-induced vascular injury as well as vital organ system failure.
Xin Shi
Kelly A Seidle
Kevin J Simms
Feng Dong
William M Chilian
Ping Zhang
Pharmacol Ther
. 2023 Jan;241:108315. doi: 10.1016/j.pharmthera.2022.108315. Epub 2022 Nov 24.
2023
English
Cardiac Pressure Overload Initiates A Systemic Stem Cell Response
& Experimental Medicine; acute myocardial-infarction; Biotechnology & Applied Microbiology; bone marrow; bone marrow; cardiac stem cells; cardiomyocytes; Cell Biology; endogenous stem cells; endothelial; endothelial progenitor cells; heart; Hematology; hypertrophy; identification; murine; peripheral-blood; progenitor cells; regeneration; Research; spleen; SSEA-1; transaortic constriction; transplantation
Finan A; Kiedrowski M; Turturice B A; Sopko N A; Penn M S
Cytotherapy
2012
2012-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.3109/14653249.2012.684380" target="_blank" rel="noreferrer noopener">10.3109/14653249.2012.684380</a>
Stimulation of Coronary Collateral Growth by Granulocyte Stimulating Factor Role of Reactive Oxygen Species
ischemia; ROS; cardiomyocytes; receptor; Cardiovascular System & Cardiology; endothelial progenitor cells; expression; Hematology; activation; angiotensin-ii; neutrophils; neovascularization; bone-marrow; coronary collateral circulation; G-CSF; G-CSF
Objective-The purpose of this study was to determine whether G-CSF promotes coronary collateral growth (CCG) and decipher the mechanism for this stimulation. Methods and Results-In a rat model of repetitive episodic myocardial ischemia (RI, 40 seconds LAD occlusion every 20 minutes for 2 hours and 20 minutes, 3 times/d for 5 days) CCG was deduced from collateral-dependent flow (flow to LAD region during occlusion). After RI, G-CSF (100 mu g/kg/d) increased CCG (P < 0.01) (0.47 +/- 0.15) versus vehicle (0.14 +/- 0.06). Surprisingly, G-CSF treatment without RI increased CCG (0.57 +/- 0.18) equal to G-CSF + RI. We evaluated ROS by dihydroethidine (DHE) fluorescence (LV injection, 60 mu g/kg, during two episodes of ischemia). DHE fluorescence was double in G-CSF + RI versus vehicle + RI (P < 0.01), and even higher in G-CSF without RI (P < 0.01). Interestingly, the DHE signal did not colocalize with myeloperoxidase (immunostaining, neutrophil marker) but appeared in cardiac myocytes. The study of isolated cardiac myocytes revealed the cytokine stimulates ROS which elicit production of angiogenic factors. Apocynin inhibited G-CSF effects both in vivo and in vitro. Conclusions-G-CSF stimulates ROS production directly in cardiomyocytes, which plays a pivotal role in triggering adaptations of the heart to ischemia including growth of the coronary collaterals. (Arterioscler Thromb Vasc Biol. 2009; 29: 1817-1822.)
Carrao A C R; Chilian W M; Yun J; Kolz C; Rocic P; Lehmann K; van den Wijngaard Jphm; van Horssen P; Spaan J A E; Ohanyan V; Pung Y F; Buschmann I
Arteriosclerosis Thrombosis and Vascular Biology
2009
2009-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1161/atvbaha.109.186445" target="_blank" rel="noreferrer noopener">10.1161/atvbaha.109.186445</a>