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May 24-25, 2018
London, UK
Vascular Surgery 2018
3
rd
Edition of World Congress & Exhibition on
Vascular Surgery
Journal of Vascular and Endovascular Therapy
ISSN: 2573-4482
Circulating proangiogenic cells (PACs), were described as bone
marrow-derivedcells that cancontribute toangiogenesisandeven
de novo blood vessel formation. Number and function of PACs
are impaired in patients with diabetes or cardiovascular diseases.
Both diseases can be accompanied by decreased levels of heme
oxygenase-1 (HMOX1), cytoprotective, heme-degrading enzyme,
which is crucial for PAC function in mouse models. Therefore, our
study aimed to check whether pharmacological enhancement of
HMOX1 expression in hematopoietic stem/progenitor (HSPC)
derived PAC cells would improve their paracrine proangiogenic
activity. We used GCSF-mobilized CD34+ cells, FACS-sorted
from a healthy donor PBMCs. Sorted cells were CD45dimCD90-
CD105-CD181- and predominantly CD133+ and CD11b-. CD34+
cells after six days in culture were stimulated with atorvastatin,
acetylsalicylic acid, sulforaphane, resveratrol or metformin for 48
h. Conditioned media from such cells were then used to stimulate
human aortic endothelial cells (HAoEC) to enhance tube-like
structure formation in Matrigel assay. The only stimulant that
enhanced PAC paracrine angiogenic activity was atorvastatin.
On the other hand, the only one that induced heme oxygenase-1
expression was sulforaphane, a known activator of HMOX1
inducer – NRF2. Moreover, none of the stimulants changed the
levels of 30 cytokines and growth factors testedwith themultiplex
test. Then, we used atorvastatin-stimulated cells or conditioned
media from them in the Matrigel plug in vivo angiogenic assay.
Neither atorvastatin alone in control media nor conditionedmedia
nor AT-stimulated cells affected numbers of endothelial cells
in the plug or plug’s vascularization. Concluding, atorvastatin
can enhance the paracrine angiogenic activity of human CD34+
HSPC-derived PAC cells in vitro, but the effect was not observed
in vivo. Moreover, the enhancement of HMOX1 expression with
sulforaphane does not influence PAC proangiogenic action
in
vitro
.
Recent Publications
1. Xie Y, Potter CMF, Le Bras A, NowakWN, GuW, Bhaloo S
I, Zhang Z, Hu Y, Zhang L and Xu Q (2017) Leptin induces
Sca-1+ progenitor cell migration enhancing neointimal
lesions in vessel-injury mouse models. Arteriosclerosis,
Thrombosis, and Vascular Biology 11:2114-2127.
2. Nowak W N, Taha H, Kachamakova Trojanowska N,
Stepniewski J, Markiewicz J A, Kusienicka A, Szade
K, Szade A, Bukowska Strakova K, Hajduk K, Klóska D,
Kopacz A, Grochot Przeczek A, Barthenheier K, Cauvin
C, Dulak J and Jozkowicz A (2017) Murine bone marrow
mesenchymal stromal cells respond efficiently to
oxidative stress despite the low level of heme oxygenase
1 and 2. Antioxidants and Redox Signal doi: 10.1089/
ars.2017.7097.
3. Langrzyk A, Nowak W N, Stępniewski J, Jaźwa A,
Florczyk-Soluch U, Józkowicz A and Dulak J (2017)
Critical view on mesenchymal stromal cells in
regenerative medicine. Antioxidants and Redox Signal
doi: 10.1089/ars.2017.7159.
4. Januszek R, Mika P, Nowobilski R, Nowak W, Kusienicka
A, Klóska D, Maga P and Niżankowski R (2017) Soluble
endoglin as a prognostic factor of the claudication
distance improvement in patients with peripheral
artery disease undergoing supervised treadmill
training program. Journal of the American Society of
Hypertension 11:553-564.
5. Kokkinopoulos I, Wong M M, Potter C M F, Xie Y, Yu
B, Warren D T, Nowak W N, Le Bras A, Ni Z, Zhou C,
Ruan X, Karamariti E, Hu Y, Zhang L and Xu Q (2017)
Adventitial SCA-1+ progenitor cell gene sequencing
reveals the mechanisms of cell migration in response to
hyperlipidemia. Stem Cell Reports 9:681-696.
Atorvastatin enhances paracrine proangiogenic activity of
hematopoietic stem/progenitor derived cells in vitro but not in vivo
Witold N Nowak, Hevidar Taha, Joanna Markiewicz, Neli Kachamakova
Trojanowska, Urszula Florczyk Soluch, Jozef Dulak
and
Alicja Jozkowicz
Jagiellonian University, Poland
Witold N Nowak et al., J Vasc Endovasc Therapy 2018, Volume 3
DOI: 10.21767/2573-4482-C1-003