Cinnamic aldehyde inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia in Zucker Diabetic Fatty rats

Autor: Edward Moreira Bahnson, Wulin Jiang, Nicholas Buglak
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Vascular smooth muscle
ZDF
Zucker Diabetic Fatty rat
Clinical Biochemistry
Cell
MPO
myeloperoxidase
030204 cardiovascular system & hematology
Biochemistry
Nrf2
nuclear factor erythroid 2-related factor 2
Antioxidants
Muscle
Smooth
Vascular
BrdU
bromodeoxyuridine
0302 clinical medicine
Restenosis
DM
diabetes mellitus
I:M
intima:media
GSH
glutathione
ARE/EpRE
antioxidant/electrophile response element
Acrolein
lcsh:QH301-705.5
Cells
Cultured
HO-1
heme oxygenase-1
SFN
sulforaphane
Neointimal hyperplasia
chemistry.chemical_classification
NOX1
NADPH oxidase 1
lcsh:R5-920
Diabetes
3. Good health
CA
cinnamic aldehyde
medicine.anatomical_structure
VSMC
vascular smooth muscle cells
lcsh:Medicine (General)
Artery
Research Paper
medicine.medical_specialty
PDGF
platelet derived growth factor
NF-E2-Related Factor 2
Cinnamic aldehyde
CVD
cardiovascular disease
Nrf2
Diabetes Complications
03 medical and health sciences
ROS
reactive oxygen species
In vivo
Internal medicine
Neointima
SOD
superoxide dismutase
medicine
Diabetes Mellitus
Vascular smooth muscle cells
Animals
Cell Proliferation
Reactive oxygen species
XO
xanthine oxidase
Hyperplasia
Cell growth
business.industry
Organic Chemistry
medicine.disease
Rats
Zucker
030104 developmental biology
Endocrinology
chemistry
lcsh:Biology (General)
Prx
peroxiredoxin
business
Tunica Intima
DHE
dihydroethidium
GCLC
glutamate-cysteine ligase catalytic subunit
Zdroj: Redox Biology, Vol 19, Iss, Pp 166-178 (2018)
Redox Biology
ISSN: 2213-2317
Popis: Atherosclerosis remains the number one cause of death and disability worldwide. Atherosclerosis is treated by revascularization procedures to restore blood flow to distal tissue, but these procedures often fail due to restenosis secondary to neointimal hyperplasia. Diabetes mellitus is a metabolic disorder that accelerates both atherosclerosis development and onset of restenosis. Strategies to inhibit restenosis aim at reducing neointimal hyperplasia by inhibiting vascular smooth muscle cell (VSMC) proliferation and migration. Since increased production of reactive oxygen species promotes VSMC proliferation and migration, redox intervention to maintain vascular wall redox homeostasis holds the potential to inhibit arterial restenosis. Cinnamic aldehyde (CA) is an electrophilic Nrf2 activator that has shown therapeutic promise in diabetic rodent models. Nrf2 is a transcription factor that regulates the antioxidant response. Therefore, we hypothesized that CA would activate Nrf2 and would inhibit neointimal hyperplasia after carotid artery balloon injury in the Zucker Diabetic Fatty (ZDF) rat. In primary ZDF VSMC, CA inhibited cell growth by MTT with an EC50 of 118 ± 7 μM. At a therapeutic dose of 100 μM, CA inhibited proliferation of ZDF VSMC in vitro and reduced the proliferative index within the injured artery in vivo, as well as migration of ZDF VSMC in vitro. CA activated the Nrf2 pathway in both ZDF VSMC and injured carotid arteries while also increasing antioxidant defenses and reducing markers of redox dysfunction. Additionally, we noted a significant reduction of neutrophils (69%) and macrophages (78%) within the injured carotid arteries after CA treatment. Lastly, CA inhibited neointimal hyperplasia evidenced by a 53% reduction in the intima:media ratio and a 61% reduction in vessel occlusion compared to arteries treated with vehicle alone. Overall CA was capable of activating Nrf2, and inhibiting neointimal hyperplasia after balloon injury in a rat model of diabetic restenosis.
Graphical abstract fx1
Highlights • CA inhibits ZDF VSMC migration and proliferation in vitro. • CA activates Nrf2 in VSMC in vitro and in injured diabetic carotid arteries. • CA increases antioxidants and reduces redox marker levels in VSMC. • CA reduces leukocytes and redox markers in injured diabetic carotid arteries. • CA reduces proliferation and intimal hyperplasia in ZDF rats after balloon injury.
Databáze: OpenAIRE
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