Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)

Hashem, R.M.; Rashed, L.A.; Abdelkader, R.M.; Hashem, K.S.

doi:10.1590/1414-431X2020e10807

Acessibilidade / Reportar erro

Brasil

Brazilian Journal of Medical and Biological Research

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Research Article • Braz. J. Med. Biol. Res. 54 (8) • 2021 • https://doi.org/10.1590/1414-431X2020e10807 copy

Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)

Authorship SCIMAGO INSTITUTIONS RANKINGS

Smooth muscle cells (SMCs) are currently considered a central pivotal player in pathogenesis and development of atherosclerotic lesions. As consequence of vascular injury, SMCs migrate from the tunica media into the tunica intima layers where they contribute to neointimal formation by converting into foam cells and producing pro-inflammatory and oxidative stress markers. We targeted the replacement of neointimal SMCs by using the mesenchymal stem cells (MSCs) therapy in experimentally induced atherosclerosis in an attempt to improve the atherosclerotic lesion and its concomitant complications. Rats were divided into 4 groups (n=20). Control group: rats kept on a standard chow diet; atherosclerotic group: rats received the atherogenic diet; stem cells-treated group: rats were injected with CD34⁺ stem cells (6×10⁶ cells in 0.5 mL PBS in rat tail vein) and maintained on the atherogenic diet; and resveratrol-treated group: rats were supplemented orally with resveratrol at a dose level 3 mg/kg per day and the atherogenic diet. After 12 weeks, rats were euthanized, blood samples were collected for separation of serum, and abdominal aortas were excised for further biochemical, molecular, and histopathological investigations. We used resveratrol, the well-established anti-atherosclerotic drug, as a benchmark to assess the efficacy of stem cell therapy. MSCs treatment revealed significant amelioration in both histopathological and biochemical patterns as evidenced by decreased foam cells formation, ICAM-1, VCAM, M-CSF, iNOS, COX-2, and TNF-α. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.

Atherosclerosis; Intracellular adhesion molecule (ICAM); Vascular cell adhesion molecule (VCAM); Smooth muscle cells; Stem cells

Groups	Cholesterol (mg/dL)	Total lipid (mg/dL)	LDL-C (mg/dL)	HDL-C (mg/dL)	TAG (mg/dL)	Atherogenic index (TAG/HDL)
Control	115.3±13.2	300.2±24.8	67.85±8.72	31.33±6.08	80.42±10.2	2.56
Atherosclerotic	250.8±23.6^a	640.5±59.7^a	175±15.6^a	39±7.22^a	160.0±17.2^a	4.1^a
Stem cells-treated	243.6±31.6^a	630±72.4^a	171.0±18.5^a	38.6±7.32^a	155.3±11.2^a	4.08^a
Resveratrol-treated	170.4±16.1^a,b	460.5±38.9^a,b	108.8±11.4^a,b	38.8±7.51^a	107.2±10.8^a,b	2.76^b

Groups	GSH (mg/g tissue)	MDA (nmol/g tissue)	TAC (mM/L)	Catalase (U/g tissue)
Control	68.28±7.54	25.98±3.48	3.1±2.55	6.23±0.43
Atherosclerotic	37.53±2.95^a	68.24±8.38^a	1.45±0.13^a	2.3±0.27^a
Stem cells-treated	59.09±5.72^b	32.96±2.81^b	2.8±0.31^b	5.55±0.47^b
Resveratrol-treated	40.2±5.31^a,b	43.57±3.68^a,b	1.6±0.18^a,b	3.15±0.26^a,b

Associação Brasileira de Divulgação Científica Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto SP Brazil, Tel. / Fax: +55 16 3315-9120 - Ribeirão Preto - SP - Brazil
E-mail: bjournal@terra.com.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Correspondence: K.S. Hashem: <khaled.mohamed2@vet.bsu.edu.eg>

COX-2	forward: 5′-ACACTCTATCACTGGCATCC-3′reverse: 5′- GAAGGGACACCCTTTCACAT-3′	Gene ID: 7751820Accession number on the chromosome: NC_012389.1
iNOS	forward: 5′-CGGTTCACAGTCTTGGTGAAAG-3′	Gene ID: 24599
	reverse: 5′-CAGGTGTTCCCCAGGTAGGTAG-3′	Accession number on chromosome: NC_005109.4
TNF-α	forward: 5′-CGTCGTAGCAAACCACCAAG-3′	Gene ID: 24835
	reverse: 5′-ACACAGAGCAATGACTCCAAAG-3′	Accession number on chromosome: NC_005119.4
β-actin	forward: 5′-ATCATGTTTGAGACCTTCAACACC-3′	Gene ID: 11461
	reverse: 5′-TAGCTCTTCTCCAGGGAGG-3′	Accession number of chromosome: NC_000071.6