Amplification of Coronary Arteriogenic Capacity of Multipotent Stromal Cells by Epidermal Growth Factor
coronary circulation; angiogenesis; collateral circulation; Cardiovascular System & Cardiology; Myocardial infarction; expression; binding; Hematology; mesenchymal stem-cells; smooth-muscle-cells; rat model; endothelial-cells; collateral growth; improve heart function
Objective-We determined whether increasing adherence of multipotent stromal cells (MSCs) would amplify their effects on coronary collateral growth (CCG). Methods and Results-Adhesion was established in cultured coronary endothelials cells (CECs) or MSCs treated with epidermal growth factor (EGF). EGF increased MSCs adhesion to CECs, and increased intercellular adhesion molecule (ICAM-1) or vascular cell adhesion molecule (VCAM-1) expression. Increased adherence was blocked by EGF receptor antagonism or antibodies to the adhesion molecules. To determine whether adherent MSCs, treated with EGF, would augment CCG, repetitive episodes of myocardial ischemia (RI) were introduced and CCG was measured from the ratio of collateral-dependent (CZ) and normal zone (NZ) flows. CZ/NZ was increased by MSCs without treatment versus RI-control and was further increased by EGF-treated MSCs. EGF-treated MSCs significantly improved myocardial function versus RI or RI + MSCs demonstrating that the increase in collateral flow was functionally significant. Engraftment of MSCs into myocardium was also increased by EGF treatment. Conclusions-These results reveal the importance of EGF in MSCs adhesion to endothelium and suggest that MSCs may be effective therapies for the stimulation of coronary collateral growth when interventions are used to increase their adhesion and homing (in vitro EGF treatment) to the jeopardized myocardium. (Arterioscler Thromb Vasc Biol. 2009; 29: 802-808.)
Belmadani S; Matrougui K; Kolz C; Pung Y F; Palen D; Prockop D J; Chilian W M
Arteriosclerosis Thrombosis and Vascular Biology
2009
2009-06
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1161/atvbaha.109.186189" target="_blank" rel="noreferrer noopener">10.1161/atvbaha.109.186189</a>
A brief etymology of the collateral circulation.
*Cardiology; *Collateral Circulation/physiology; *Terminology as Topic; Blood Vessels/embryology/growth & development; collateral circulation; Humans; myocardial ischemia; Neovascularization; peripheral arterial disease; Physiologic/physiology; stroke
It is well known that the protective capacity of the collateral circulation falls short in many individuals with ischemic disease of the heart, brain, and lower extremities. In the past 15 years, opportunities created by molecular and genetic tools, together with disappointing outcomes in many angiogenic trials, have led to a significant increase in the number of studies that focus on: understanding the basic biology of the collateral circulation; identifying the mechanisms that limit the collateral circulation's capacity in many individuals; devising methods to measure collateral extent, which has been found to vary widely among individuals; and developing treatments to increase collateral blood flow in obstructive disease. Unfortunately, accompanying this increase in reports has been a proliferation of vague terms used to describe the disposition and behavior of this unique circulation, as well as the increasing misuse of well-ensconced ones by new (and old) students of collateral circulation. With this in mind, we provide a brief glossary of readily understandable terms to denote the formation, adaptive growth, and maladaptive rarefaction of collateral circulation. We also propose terminology for several newly discovered processes that occur in the collateral circulation. Finally, we include terms used to describe vessels that are sometimes confused with collaterals, as well as terms describing processes active in the general arterial-venous circulation when ischemic conditions engage the collateral circulation. We hope this brief review will help unify the terminology used in collateral research.
Faber James E; Chilian William M; Deindl Elisabeth; van Royen Niels; Simons Michael
Arteriosclerosis, thrombosis, and vascular biology
2014
2014-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1161/ATVBAHA.114.303929" target="_blank" rel="noreferrer noopener">10.1161/ATVBAHA.114.303929</a>
Failure Of Regenerative Cell-based Therapy To Stimulate Coronary Collateral Growth In A Rat Model Of Metabolic Syndrome
Arteriogenesis; Cardiovascular System & Cardiology; Collateral circulation; Metabolic; oxidative stress; Stem cell therapy; syndrome
Logan S; Chilian W M; Ohanyan V A; Stevanov K; Enrick M; Kolz C L; Yin L Y
Circulation
2012
2012-11
Journal Article or Conference Abstract Publication
n/a
Mitochondrial oxidative stress corrupts coronary collateral growth by activating adenosine monophosphate activated kinase-alpha signaling.
AMP-Activated Protein Kinases/*metabolism; Animal; Animals; Body Weight/physiology; Cells; collateral circulation; coronary circulation; Coronary Vessels/cytology/*enzymology; Cultured; Disease Models; Endothelial Cells/cytology/*enzymology; Humans; Inbred WKY; Ischemia/metabolism/pathology; mitochondria; Mitochondria/drug effects/*metabolism; Myocardium/enzymology/pathology; Oxidative Stress/*physiology; Rats; reactive oxygen species; Rotenone/pharmacology; Signal Transduction/*physiology; TOR Serine-Threonine Kinases/metabolism; Uncoupling Agents/pharmacology
OBJECTIVE: Our goal was to determine the mechanism by which mitochondrial oxidative stress impairs collateral growth in the heart. APPROACH AND RESULTS: Rats were treated with rotenone (mitochondrial complex I inhibitor that increases reactive oxygen species production) or sham-treated with vehicle and subjected to repetitive ischemia protocol for 10 days to induce coronary collateral growth. In control rats, repetitive ischemia increased flow to the collateral-dependent zone; however, rotenone treatment prevented this increase suggesting that mitochondrial oxidative stress compromises coronary collateral growth. In addition, rotenone also attenuated mitochondrial complex I activity and led to excessive mitochondrial aggregation. To further understand the mechanistic pathway(s) involved, human coronary artery endothelial cells were treated with 50 ng/mL vascular endothelial growth factor, 1 micromol/L rotenone, and rotenone/vascular endothelial growth factor for 48 hours. Vascular endothelial growth factor induced robust tube formation; however, rotenone completely inhibited this effect (P\textless0.05 rotenone versus vascular endothelial growth factor treatment). Inhibition of tube formation by rotenone was also associated with significant increase in mitochondrial superoxide generation. Immunoblot analyses of human coronary artery endothelial cells with rotenone treatment showed significant activation of adenosine monophosphate activated kinase (AMPK)-alpha and inhibition of mammalian target of rapamycin and p70 ribosomal S6 kinase. Activation of AMPK-alpha suggested impairments in energy production, which was reflected by decrease in O2 consumption and bioenergetic reserve capacity of cultured cells. Knockdown of AMPK-alpha (siRNA) also preserved tube formation during rotenone, suggesting the negative effects were mediated by the activation of AMPK-alpha. Conversely, expression of a constitutively active AMPK-alpha blocked tube formation. CONCLUSIONS: We conclude that activation of AMPK-alpha during mitochondrial oxidative stress inhibits mammalian target of rapamycin signaling, which impairs phenotypic switching necessary for the growth of blood vessels.
Pung Yuh Fen; Sam Wai Johnn; Stevanov Kelly; Enrick Molly; Chen Chwen-Lih; Kolz Christopher; Thakker Prashanth; Hardwick James P; Chen Yeong-Renn; Dyck Jason R B; Yin Liya; Chilian William M
Arteriosclerosis, thrombosis, and vascular biology
2013
2013-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1161/ATVBAHA.113.301591" target="_blank" rel="noreferrer noopener">10.1161/ATVBAHA.113.301591</a>
Induced Vascular Progenitor Cells Derived From Endothelial Cells Stimulate Coronary Collateral Growth
Cardiovascular System & Cardiology; Collateral circulation
Yin L Y; Ohanyan V; Pung Y F; Delucia A L; Bailey E; Enrick M; Stevanov K; Kolz C L; Guarini G; Chilian W
Circulation
2011
2011-11
Journal Article
n/a