Arteriogenesis Proceeds via ICAM-1/Mac-1- Mediated Mechanisms

Hoefer, Imo E.; Royen, Niels van; Rectenwald, John E.; Deindl, Elisabeth; Hua, Jing; Jost, Marco; Grundmann, Sebastian; Voskuil, Michiel; Ozaki, C. Keith; Piek, Jan J.; Buschmann, Ivo

doi:10.1161/01.res.0000126922.18222.f0

Cited by 158 publications

(144 citation statements)

References 40 publications

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…Here, DNMT1 inhibition increased arteriogenic capacity by ≈44% in nonreversed segments, while there was no effect on reversed flow segments ( P =0.163), indicating that this response is not limited to the C57BL/6 strain. We also sought to determine whether this increased arteriogenic capacity in nonreversed flow segments following DNMT1 inhibition corresponded to altered macrophage recruitment, a necessary component of collateral artery growth45, 46, 47, 48, 49, 50, 52 in vivo. Nonreversed flow collateral segments exhibited a trend ( P =0.057) toward increased pericollateral Mac3 + macrophages in 5AZA‐treated mice (day 17 post FAL, 3 days of 5AZA treatment), corresponding to our previous in vitro results (Figure S7).…”

Section: Resultsmentioning

confidence: 99%

DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point

Heuslein

Gorick

Song

et al. 2017

JAHA

View full text Add to dashboard Cite

BackgroundArteriogenesis is initiated by increased shear stress and is thought to continue until shear stress is returned to its original “set point.” However, the molecular mechanism(s) through which shear stress set point is established by endothelial cells (ECs) are largely unstudied. Here, we tested the hypothesis that DNA methyltransferase 1 (DNMT1)–dependent EC DNA methylation affects arteriogenic capacity via adjustments to shear stress set point.Methods and ResultsIn femoral artery ligation–operated C57BL/6 mice, collateral artery segments exposed to increased shear stress without a change in flow direction (ie, nonreversed flow) exhibited global DNA hypermethylation (increased 5‐methylcytosine staining intensity) and constrained arteriogenesis (30% less diameter growth) when compared with segments exposed to both an increase in shear stress and reversed‐flow direction. In vitro, ECs exposed to a flow waveform biomimetic of nonreversed collateral segments in vivo exhibited a 40% increase in DNMT1 expression, genome‐wide hypermethylation of gene promoters, and a DNMT1‐dependent 60% reduction in proarteriogenic monocyte adhesion compared with ECs exposed to a biomimetic reversed‐flow waveform. These results led us to test whether DNMT1 regulates arteriogenic capacity in vivo. In femoral artery ligation–operated mice, DNMT1 inhibition rescued arteriogenic capacity and returned shear stress back to its original set point in nonreversed collateral segments.ConclusionsIncreased shear stress without a change in flow direction initiates arteriogenic growth; however, it also elicits DNMT1‐dependent EC DNA hypermethylation. In turn, this diminishes mechanosensing, augments shear stress set point, and constrains the ultimate arteriogenic capacity of the vessel. This epigenetic effect could impact both endogenous collateralization and treatment of arterial occlusive diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point

Heuslein

Gorick

Song

et al. 2017

JAHA

View full text Add to dashboard Cite

show abstract

“…We also examined surface adhesion molecule expression on circulating monocytes by flow cytometry and on the aortic endothelium by immunohistochemistry, because several of these molecules have been shown to be critically important in monocyte recruitment into vessel walls (22,28,35,46). The selectin group of adhesion molecules are involved in monocyte rolling and tethering to activated endothelium, while the integrins (CD18/CD11, VLA-4) are required for firm adhesion to proteoglycans and immunoglobulin molecules (ICAM-1 and VCAM-1) on the vascular endothelium.…”

Section: Discussionmentioning

confidence: 99%

“…In the process of monocyte recruitment, changes in adhesion molecules on monocytes are involved in leukocyte tethering, rolling (E-and L-selectin), firm adhesion (CD11/CD18 integrins), and transmigration [very late antigen (VLA)-4, platelet endothelial cell adhesion molecule (PECAM)-1] by interacting with molecules on the endothelium [intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM) -1]. The expression of these various surface antigens is modulated by inflammatory cytokines (22,28,35,46).…”

mentioning

confidence: 99%

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques

Yatera

Hsieh²,

Hogg³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

demiologic studies have shown an association between exposure to ambient particulate air pollution Ͻ10 m in diameter (PM10) and increased cardiovascular morbidity and mortality. We previously showed that PM10 exposure causes progression of atherosclerosis in coronary arteries. We postulate that the recruitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM10-induced acceleration of atherosclerosis. The study objective was to quantify the recruitment of circulating monocytes into vessel walls and the progression of atherosclerotic plaques induced by exposure to PM10. Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM10 (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo-2Ј-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM10 caused progression of atherosclerotic lesions in thoracic and abdominal aorta. It also decreased circulating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platelet endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 ␣-chain), and increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM10 increased the number of BrdU-labeled monocytes adherent to endothelium over plaques and increased the migration of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conclude that exposure to ambient air pollution particles promotes the recruitment of circulating monocytes into atherosclerotic plaques and speculate that this is a critically important step in the PM10-induced progression of atherosclerosis. atherosclerosis; adhesion molecules EPIDEMIOLOGIC STUDIES have associated exposure to ambient particulate air pollution Ͻ10 m in diameter (PM 10

show abstract

“…In recent studies, we have shown that Icam1 is differentially expressed during arteriogenesis and that blunted Icam1 expression as well as Icam1 deficiency is associated with less effective arteriogenesis and perivascular accumulation of macrophages. [4][5][6] In the current study, our qRT-PCR results demonstrated that administration of nor-NOHA abolished the differential expression of Icam1 in growing collaterals. These data are in accordance with results from Giri et al 31 showing that downregulation of arginase 2 in human umbilical vein endothelial cells abrogated leukocyte adhesion by blocking the expression of Icam1.…”

Section: Arginase Inhibition In Arteriogenesismentioning

confidence: 62%

“…3 Animal models, mainly for peripheral arteriogenesis, evidenced that increased shear stress results in activation of the arteriolar endothelium with subsequent upregulation of monocyte chemoattractant protein-1 (MCP-1) as well as ICAM1 presenting the prerequisite for monocyte recruitment, adhesion, and extravasation. [4][5][6] After extravasation, monocytes mature to macrophages, whereby M1 as well as M2 macrophages have been described to contribute to vascular remodeling. 7 Interestingly, it has been shown that exogenously administrated nitric oxide (NO) donors promote arteriogenesis.…”

mentioning

confidence: 99%

Arginase inhibition attenuates arteriogenesis and interferes with M2 macrophage accumulation

Lasch¹,

Caballero-Martinez²,

Troidl

et al. 2016

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

L-Arginine is the common substrate for nitric oxide synthases (NOS) and arginase. Whereas the contribution of NOS to collateral artery growth (arteriogenesis) has been demonstrated, the functional role of arginase remains to be elucidated and was topic of the present study. Arteriogenesis was induced in mice by ligation of the femoral artery. Laser Doppler perfusion measurements demonstrated a significant reduction in arteriogenesis in mice treated with the arginase inhibitor nor-NOHA (N ω -hydroxy-nor-arginine). Accompanying in vitro results on murine primary arterial endothelial cells and smooth muscle cells revealed that nor-NOHA treatment interfered with cell proliferation and resulted in increased nitrate/ nitrite levels, indicative for increased NO production. Immuno-histological analyses on tissue samples demonstrated that nor-NOHA administration caused a significant reduction in M2 macrophage accumulation around growing collateral arteries. Gene expression studies on isolated growing collaterals evidenced that nor-NOHA treatment abolished the differential expression of Icam1 (intercellular adhesion molecule 1). From our data we conclude that arginase activity is essential for arteriogenesis by promoting perivascular M2 macrophage accumulation as well as arterial cell proliferation.

show abstract

Arteriogenesis Proceeds via ICAM-1/Mac-1- Mediated Mechanisms

Cited by 158 publications

References 40 publications

DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point

DNA Methyltransferase 1–Dependent DNA Hypermethylation Constrains Arteriogenesis by Augmenting Shear Stress Set Point

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques

Arginase inhibition attenuates arteriogenesis and interferes with M2 macrophage accumulation

Contact Info

Product

Resources

About