Different Drugs Effect on Mesenchymal Stem Cells Isolated From Abdominal Aortic Aneurysm

被引:4
|
作者
Pini, Rodolfo [1 ]
Ciavarella, Carmen [2 ]
Faggioli, Gianluca [1 ]
Gallitto, Enrico [1 ]
Indelicato, Giuseppe [1 ]
Fenelli, Cecilia [1 ]
Mascoli, Chiara [1 ]
Vacirca, Andrea [1 ]
Gargiulo, Mauro [1 ]
Pasquinelli, Gianandrea [2 ]
机构
[1] Univ Bologna, Dept Expt Diagnost & Special Med Dimes, Vasc Surg, Bologna, Italy
[2] Univ Bologna, Dept Expt Diagnost & Special Med DIMES, Clin Pathol, Bologna, Italy
关键词
PPAR-GAMMA; PATHOGENESIS; ACTIVATION; EXPRESSION; GROWTH; MODEL; RAT;
D O I
10.1016/j.avsg.2020.03.001
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background: Abdominal aortic aneurysm (AAA) is a progressive dilation of the aortic wall, determined by the unbalanced activity of matrix metalloproteinase (MMPs). In vitro and in vivo studies support the pivotal role of MMP-9 to AAA pathogenesis. In our experience, we elucidated the expression of MMP-9 in an ex vivo model of human mesenchymal stem cells isolated from AAA specimen (AAA-MSCs). Thus, MMP-9 inhibition could be an attractive therapeutic strategy for inhibiting AAA degeneration and rupture. Our study was aimed at testing the effect of 3 different drugs (pioglitazone, doxycycline, simvastatin) on MMP-9 and peroxisome proliferator-activated receptor (PPAR)-gamma expression in AAA-MSCs. Methods: Aneurysmal aortic wall segments were taken from AAA patients after the open surgical treatment. MSCs were isolated from AAA (n = 20) tissues through enzymatic digestion. AAA-MSCs were exposed to different doses of pioglitazone (5-10-25 mu M), doxycycline (10-25 mu M), and simvastatin (10 mu M) for 24 h. The effect of each drug was evaluated in terms of cell survival, by crystal violet stain. MMP-9 and PPAR-gamma mRNA were analyzed using real-time PCR. Results: AAA-MSCs were not affected by the exposure to the selected drugs, as shown by the analysis of cell viability. Interestingly, MMP-9 mRNA resulted significantly decreased after each treatment, recording a downregulation of 50% in presence of pioglitazone, 90% with doxycycline, and 40% with exposed to simvastatin, in comparison to untreated cells. We further analyzed the expression of PPAR-gamma target of pioglitazone, observing an upregulation in exposed AAA-MSCs to controls. Conclusions: Our data support the potential therapeutic effect of pioglitazone, doxycycline, and simvastatin on AAA by reducing the MMP-9 expression in a patient-specific model (AAA-MSCs). In addition, pioglitazone drives the increase of PPAR-G, another promising target for AAA therapy. Further studies are necessary to elucidate the mechanism driving this inhibitory pathway, which can reduces the mortality risk associated with AAA rupture.
引用
收藏
页码:490 / 496
页数:7
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