Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration

Ferri, Nicola; Panariti, Federica; Ricci, Chiara; Maiocchi, G.; Corsini, Alberto

doi:10.1177/1470320314528364

Cited by 4 publications

(3 citation statements)

References 40 publications

(51 reference statements)

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“…Myofibroblast migration was detected with a modified Boyden's chamber assay [13]. The cell culture inserts, which contain membranes with 8.0 lm pore size, were placed in a 24-well tissue culture plate (Millipore ECM508, Billerica, MA).…”

Section: Effect Of Vegf-d On Myofibroblast Migrationmentioning

confidence: 99%

Vascular endothelial growth factor-D mediates fibrogenic response in myofibroblasts

Zhao

Wei

et al. 2016

Mol Cell Biochem

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Vascular endothelial growth factor (VEGF)-D is a crucial mediator of angiogenesis. Following myocardial infarction (MI), cardiac VEGF-D and VEGF receptor (VEGFR)-3 are significantly upregulated. In addition to endothelial cells, myofibroblasts at the site of MI highly express VEGFR-3, implicating the involvement of VEGF-D in cardiac fibrogenesis that promotes repair and remodeling. The aim of the current study was to further explore the critical role of VEGF-D in fibrogenic response in myofibroblasts. Myofibroblast proliferation, migration, collagen synthesis, and degradation were investigated in cultured cardiac myofibroblasts subjected to VEGF-D with/without VEGFR antagonist or ERK inhibitor. Vehicle-treated cells served as controls. Myofibroblast proliferation and migration were detected by BrdU assay and Boyden Chamber method, respectively. Expression of type I collagen, metalloproteinase (MMP)-2/-9, tissue inhibitor of MMP (TIMP)-1/-2, and ERK phosphorylation were evaluated by Western blot analyses. Our results revealed that compared to controls, (1) VEGF-D significantly increased myofibroblast proliferation and migration; (2) VEGF-D significantly upregulated type I collagen synthesis in a dose- and time-dependent manner; (3) VEGFR antagonist abolished VEGF-D-induced myofibroblast proliferation and type I collagen release; (4) VEGF-D stimulated MMP-2/-9 and TIMP-1/-2 synthesis; (5) VEGF-D activated ERK phosphorylation; and (6) ERK inhibitor abolished VEGF-D-induced myofibroblast proliferation and type I collagen synthesis. Our in vitro studies have demonstrated that VEGF-D serves as a crucial profibrogenic mediator by stimulating myofibroblast growth, migration and collagen synthesis. Further studies are underway to determine the role of VEGF-D in fibrous tissue formation during cardiac repair following MI.

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Section: Effect Of Vegf-d On Myofibroblast Migrationmentioning

confidence: 99%

Vascular endothelial growth factor-D mediates fibrogenic response in myofibroblasts

Zhao

Wei

et al. 2016

Mol Cell Biochem

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“…We attempted to measure active RAC1 and RHOA in migrating ENCDC using sensitive G-LISA kits (Ferri et al, 2014; Nini and Dagnino, 2010), but could not obtain reproducible results. Furthermore, we wanted to measure RAC1 and RHOA activity only in cells that migrated furthest from cultured gut slices (i.e., distal ENCDC, Supplemental Figure 1) because these cells were examined for all other studies.…”

Section: Resultsmentioning

confidence: 99%

Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse

Schill

Lake

Tusheva

et al. 2016

Developmental Biology

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Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/− mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children.

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“…NP ALIS also significantly decreased collagen content in the aorta. Ferri et al [38] demonstrated the inhibitory action of aliskiren on smooth muscle cell migration induced by prorenin. The inhibitory effect of aliskiren on fibroblast proliferation in AGT-REN double transgenic hypertensive mice in vitro has been documented as well [39].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Nanoparticle-Loaded Aliskiren on Cardiovascular System in Spontaneously Hypertensive Rats

et al. 2019

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Aliskiren, a renin inhibitor, has been shown to have cardioprotective and blood pressure (BP) lowering effects. We aimed to determine the effects of nanoparticle-loaded aliskiren on BP, nitric oxide synthase activity (NOS) and structural alterations of the heart and aorta developed due to spontaneous hypertension in rats. Twelve week-old male spontaneously hypertensive rats (SHR) were divided into the untreated group, group treated with powdered or nanoparticle-loaded aliskiren (25 mg/kg/day) and group treated with nanoparticles only for 3 weeks by gavage. BP was measured by tail-cuff plethysmography. NOS activity, eNOS and nNOS protein expressions, and collagen content were determined in both the heart and aorta. Vasoactivity of the mesenteric artery and wall thickness, inner diameter, and cross-sectional area (CSA) of the aorta were analyzed. After 3 weeks, BP was lower in both powdered and nanoparticle-loaded aliskiren groups with a more pronounced effect in the latter case. Only nanoparticle-loaded aliskiren increased the expression of nNOS along with increased NOS activity in the heart (by 30%). Moreover, nanoparticle-loaded aliskiren decreased vasoconstriction of the mesenteric artery and collagen content (by 11%), and CSA (by 25%) in the aorta compared to the powdered aliskiren group. In conclusion, nanoparticle-loaded aliskiren represents a promising drug with antihypertensive and cardioprotective effects.

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Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration

Abstract: Taken together, we provide the first evidence of the inhibitory action of aliskiren on SMC migration induced by prorenin.

Cited by 4 publications

References 40 publications

Vascular endothelial growth factor-D mediates fibrogenic response in myofibroblasts

Vascular endothelial growth factor-D mediates fibrogenic response in myofibroblasts

Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse

Protective Effects of Nanoparticle-Loaded Aliskiren on Cardiovascular System in Spontaneously Hypertensive Rats

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