Inhibition of Thrombin Receptor Signaling on α-Smooth Muscle Actin ⁺ CD34 ⁺ Progenitors Leads to Repair After Murine Immune Vascular Injury

Abstract

Objective-The goal of this study was to use mice expressing human tissue factor pathway inhibitor (TFPI) on ␣-smooth muscle actin (␣-SMA) ϩ cells as recipients of allogeneic aortas to gain insights into the cellular mechanisms of intimal hyperplasia (IH ϩ cells were mobilized in significant numbers after allogeneic transplantation, the majority showing sustained expression of tissue factor and protease-activated receptor-1 (PAR-1). In WT, most were CD45 ϩ myeloid progenitors coexpressing CD31, vascular endothelial growth factor receptor-2 and E-selectin; 10% of these cells coexpressed ␣-SMA and were recruited to the neointima. In contrast, the ␣-SMA

Expression of Human Tissue Factor Pathway Inhibitor on Vascular Smooth Muscle Cells Inhibits Secretion of Macrophage Migration Inhibitory Factor and Attenuates Atherosclerosis in ApoE −/− Mice

“…12 Simply, a 5-mm segment of the infrarenal donor (MIF −/− mice, 15 C57BL/6 [Harlan Olac, Bicester, UK] mice, α-TFPI-Tg mice, or mice deficient in PAR-1 or -2 [The Jackson Laboratory]) aorta, flushed with 300 μL saline containing 50 U heparin, was transplanted into ApoE −/− recipients. Blood flow was confirmed by direct inspection after clamp removal.…”

“…10,12,17 Briefly, tissues were snap-frozen in dry ice, embedded in optimum cutting temperature compound (VWR International, Dorset, UK), sectioned at 5-μm thickness, and fixed in methanol at -20°C. Frozen sections were immersed in 1% BSA-PBS for 30 minutes and then incubated overnight at 4°C with the antibodies defined in the online-only Data Supplement.…”

“…We have previously defined the role that coagulation proteases play in the development of arteriosclerosis after endoluminal injury or allogeneic transplantation [10][11][12][13] using a strain of transgenic mice expressing a membrane-tethered human TF pathway inhibitor (hTFPI) fusion protein on α-smooth muscle actin (SMA)-positive cells (α-TFPI-Tg mice). Here, we crossed α-TFPI-Tg mice with apolipoprotein E-deficient (ApoE −/− ) mice to generate a new strain (ApX4) to explore how inhibition of TF on SMCs influences the development of atherosclerosis.…”

Effects of Long-Term Type I Interferon on the Arterial Wall and Smooth Muscle Progenitor Cells Differentiation

“…Whatever the source, a recent study demonstrated that targeting SM-α-actin and CD34-expressing cells could inhibit intimal hyperplasia and promote regenerative repair of the artery. 41 Thus, targeting these SM-α-actin and CD34-positive cells may be a potential treatment to prevent atherosclerosis, this may be especially relevant in patients with lupus with elevated levels of IFN-I.…”

Stem/Progenitor Cells in Vascular Regeneration

“…4 In this regard, many recent publications in ATVB have provided further insight into the functional role of stem/ progenitor cells in (1) rescuing ischemic tissues, [5][6][7][8][9][10] (2) the stem cell-derived smooth muscle accumulation in neointima, and (3) the stem cell differentiation into vascular lineages. [11][12][13][14] In the present article, we will highlight these recent publications within a brief context of the literature on vascular stem/ progenitor cells.…”