Increased number and function of endothelial progenitor cells stimulate angiogenesis by resident liver sinusoidal endothelial cells (SECs) in cirrhosis through paracrine factors

Abstract Background Endothelial microvascular dysfunction is a known mechanism of injury in cardiac amyloidosis (CA), but evidence regarding the level and function of endothelial progenitor cells (EPCs) in patients with CA is lacking. Methods Study population included patients with light-chain or transthyretin (ATTR) CA. Patients with diagnosed heart failure and preserved ejection fraction (HFpEF) without monoclonal gammopathy and a 99mTc-DPD scan incompatible with TTR were used as controls. Blood circulating EPCs were assessed quantitatively by the expression of VEGFR-2(+), CD34(+) and CD133(+) using flow cytometry, and functionally by the formation of colony forming units (CFUs). MTT assay was used to demonstrate cell viability. Tests were repeated 3 months following the initiation of amyloid-suppressive therapies (either ATTR-stabilizer or targeted chemotherapy) in CA patients. Results Our preliminary cohort included 14 CA patients (median age 74 years, 62% ATTR CA). Patients with CA vs. patients with HFpEF (n=8) demonstrated lower expression of CD34(+)/VEGFR-2(+) cells [0.51% (IQR 0.4, 0.7) vs. 1.03% (IQR 0.6, 1.4), P=0.043] and CD133(+)/VEGFR-2(+) cells [0.35% (IQR 0.23, 0.52) to 1.07% (IQR 0.6, 1.5), P=0.003]. Functionally, no differences were noted between groups. Following the initiation of amyloid-suppressive therapies in CA patients, we observed the up-regulation of CD34(+)/VEGFR-2(+) cells [2.47% (IQR 2.1, 2.7), P<0.001] and CD133(+)/VEGFR-2(+) cells [1.38% (IQR 1.1, 1.7), P=0.003]. Moreover, functionally, active EPCs were evident microscopically by their ability to form colonies (from 0.5 CFUs [IQR 0, 1.5) to 2 CFUs (IQR 1, 3.5), P=0.023]. EPCs' viability was demonstrated by an MTT assay [0.12 (IQR 0.04, 0.12) to 0.24 (IQR 0.16, 0.3), p=0.014]. Conclusions These preliminary results demonstrate reduced EPCs levels in CA patients indicating significant microvascular impairment. Amyloid-targeted therapies induce the activation of EPCs, thus possibly promoting endothelial regeneration. These findings may represent a novel mechanism of action of amyloid-suppressive therapies EPCs in CA patients and during therapy Funding Acknowledgement Type of funding source: None

Download Full-text

Surface-Bound Vascular Endothelial Growth Factor Promotes Prolonged Activation of Endothelial Cells: A New Technology for Capturing Endothelial Progenitor Cells by Intravascular Stents

Journal of Tissue Science & Engineering ◽

10.4172/2157-7552.1000140 ◽

2014 ◽

Vol 05 (02) ◽

Cited By ~ 2

Author(s):

Shotoku Tagawa Takehisa Matsuda

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

New Technology ◽

Vascular Endothelial ◽

Endothelial Progenitor ◽

Intravascular Stents ◽

Endothelial Growth Factor

Download Full-text

Presence of endothelial progenitor cells, distinct from mature endothelial cells, within human CD146+ blood cells

Thrombosis and Haemostasis ◽

10.1160/th05-07-0499 ◽

2005 ◽

Vol 94 (12) ◽

pp. 1270-1279 ◽

Cited By ~ 82

Author(s):

Bruno Delorme ◽

Agnès Basire ◽

Carla Gentile ◽

Florence Sabatier ◽

Frédéric Monsonis ◽

...

Keyword(s):

Endothelial Cells ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Network Formation ◽

Mononuclear Cells ◽

Circulating Endothelial Cells ◽

Endothelial Progenitor ◽

Color Flow ◽

Immunodeficient Mice ◽

Circulating Cells

SummaryCD146 is an adhesion molecule present on endothelial cells throughout the vascular tree. CD146 is also expressed by circulating endothelial cells (CECs) widely considered to be mature endothelial cells detached from injured vessels. The discovery of circulating endothelial progenitor cells (EPCs) originating from bone marrow prompted us to investigate whether CD146 circulating cells could also contains EPCs. We tested this hypothesis using an approach combining elimination of CECs by an adhesion step, followed by immunomagnetic sorting of remaining CD146+ cells from the non adherent fraction of cord blood mononuclear cells. When cultured under endothelial-promoting conditions, these cells differentiated as late outgrowth endothelial colonies: they grew as a cobblestone monolayer, were uniformly positive for endothelial markers and did not express leukocyte antigens. They highly proliferated and were expanded in long-term culture without alterations of their phenotypic and functional properties (DiI-ac-LDL uptake, wound repair, capillary-like network formation, and TNFα response). Moreover, these cells colonized a Matrigel plug in immunodeficient mice (NOD/SCID). Finally, using 4-color flow cytometry analysis of purified CD34+ cells, we clearly discriminated, CD146+ EPCs (CD146+ CD34+ CD45+ CD133+ or CD117+), and CD146+ CECs (CD146+ CD34+, CD45− CD133− or CD117−), both in cord and adult peripheral blood. The relative proportions of the two CD146+ subsets varied in patients with myocardial infarction as compared to healthy subjects. Our study establishes that, beside CECs, CD146+ circulating cells contain a subpopulation of EPCs with potential use in proangiogenic therapy. In addition, the dual measurement of CD146+ CECs and CD146+ EPCs offers a promising tool for monitoring vascular injury/regeneration processes in clinical situations.

Download Full-text