Dataset Information

The effect of opioid system inhibition on the Hmmr and Col1a1/ Col3a1 gene expression in relation to atherosclerotic plaque formation in aorta.

ABSTRACT: Atherosclerosis is the most common cardiovascular disease, leading to complications such as myocardial infarction and stroke, the main but not the only causes of which are lipid accumulation and inflammation. In this study, we investigated whether opioid receptor blockade impacts factors involved in atherosclerosis development and examined the expression of the Hmmr gene as a potential new factor playing a role in the development of this disease. We administered naloxone (NLX) to 8-week-old and 36-week-old ApoE-/- mice, then examined the expression of Hmmr, Col1a1, and Col3a1 in the aorta, as well as the influence of NLX administration on aortic collagen layer thickness and proteomic changes in the aorta. Additionally, we assessed the impact of NLX on the splenic T cell populations. The results showed reduced Hmmr expression in the aortas of both 8-week-old and 36-week-old mice. Col1a1 expression remained unchanged, while col3a1 expression decreased in young mice but increased in older mice. In 36-week-old mice, NLX administration led to an increase in aortic collagen layer thickness. HMMR expression on T cells increased in 36-week-old mice but remained unchanged in 8-week-old mice. Proteomic analysis identified 587 proteins that were altered following NLX treatment. Our studies suggest that both the opioid system and the Hmmr gene are important factors in atherosclerosis development.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Aorta

SUBMITTER: Aneta Stachowicz

LAB HEAD: Dominik Skiba

PROVIDER: PXD064451 | Pride | 2025-10-27

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20240221_143301_D.Skiba_aorta_powt_DirectDIA_with_library_runs_without_K2.sne	Other
	DIA_K10_aorta_powt.raw	Raw
	DIA_K12_aorta_powt.raw	Raw
	DIA_K4_aorta_powt.raw	Raw
	DIA_K5_aorta_powt.raw	Raw

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Publications

Opioid System Antagonism Alters Vascular Proteome and Collagen Deposition in ApoE-/- Mice.

Jaskuła Kinga K Nawrocka Agata A Poznański Piotr P Stachowicz Aneta A Łazarczyk Marzena M Sacharczuk Mariusz M Skiba Dominik S DS

Cells 20251008 19

Atherosclerosis is common cardiovascular disease, leading to complications such as myocardial infarction and stroke. The main causes of these diseases are lipid accumulation and inflammation in large arteries. In this study, we investigated whether opioid receptor blockade impacts factors involved in atherosclerosis development. We administered naloxone to 8-week-old and 36-week-old ApoE-/- mice, then examined the expression of Col1a1, and Col3a1 in the aorta, as well as ...[more]

PMID: 41090787

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Project description:Atherosclerosis is a chronic inflammatory condition of our arteries and the main underlying pathology of myocardial infarction and stroke. The pathogenesis is age-dependent, but the links between disease progression, age, and atherogenic cytokines and chemokines are incompletely understood. Here, we studied the chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) in atherogenic Apoe–/– mice across different stages of aging and cholesterol-rich high-fat diet (HFD). MIF promotes atherosclerosis by mediating leukocyte recruitment, lesional inflammation, and suppressing atheroprotective B- cells. However, links between MIF and advanced atherosclerosis across aging have not been systematically explored. We compared effects of global Mif-gene deficiency in 30-, 42-, and 48-week-old Apoe–/– mice on HFD for 24, 36, or 42 weeks, respectively, and in 52-week- old mice on a 6-week HFD. Mif-deficient mice exhibited reduced atherosclerotic lesions in the 30/24- and 42/36-week-old groups, but atheroprotection, which in the applied Apoe–/– model was limited to lesions in the brachiocephalic artery and abdominal aorta, was not detected in the 48/42- and 52/6-week-old groups. This suggested that atheroprotection afforded by global Mif-gene deletion differs across aging stages and atherogenic diet duration. To characterize this phenotype and study the underlying mechanisms, we determined immune cells in the periphery and vascular lesions, obtained a multiplex cytokine/chemokine profile, and compared the transcriptome between the age-related phenotypes. We found that Mif- deficiency promotes lesional macrophage and T cell counts in younger but not aged mice, with sub-group analysis pointing towards a role for Trem2+ macrophage. The transcriptomic analysis identified MIF- and aging-dependent changes in lipid, cell respiration, and inflammation pathways, and key enriched genes such as Cpne7, Cd6, Plin1, Cd274 hinting towards effects on lesional T cells, lipids, and foamy macrophages. Moreover, Mif-deficient aged mice exhibited a distinct plasma cytokine/chemokine signature consistent with the notion that mediators known to drive inflamm’aging are either not down-regulated or even up- regulated in Mif-deficient aged mice compared to the corresponding younger ones. Lastly, Mif-deficiency favored formation of lymphocyte-rich peri-adventitial leukocyte clusters. While the causative contributions of these mechanistic pillars and their interplay will be subject to future scrutiny, our study suggests that atheroprotection due to global Mif-gene deficiency in atherogenic Apoe–/– mice is reduced upon advanced aging and identifies previously unrecognized cellular and molecular targets that could explain this phenotype shift. These observations enhance our understanding of inflamm’aging and MIF pathways in atherosclerosis and may have implications for translational MIF-directed strategies.

Project description:Atherosclerosis is the preliminary cause of coronary artery disease, one of the diseases that ac-count for the largest number of fatal mortalities. Physical activity is an effective strategy to restrain atherosclerosis from deterioration. Evidence indicated that the changes of proteomic profile is highly associated with the atherosclerosis development, but the mechanism behind the exercise for atherosclerosis amelioration has not yet been investigated from the proteomics perspective. Hence, the proteomic profiles could further elucidate the systematic effects of exercise interven-tion on ApoE knockout atherosclerotic model and high fat diet intervention. In current study, Apoeem1Narl/Narl mice were randomly allocated into a normal diet (ND), western diet (WD) and WD with 12 weeks exercise intervention (WD EX) groups. The plasm proteome between WD and WD EX demonstrate the significant difference, and ten major pathways, including cardiovascular disease (CVD)–hematological disease, cellular compromise–inflammatory response, protein synthesis, connective tissue disorders, cellular movement–immune cell tracking, inflammatory response, etc., were generated by the IPA analysis. The fourteen proteins (PROS, PROZ, C2, F5, C5, SERPINA 10, FGB, FGG, CFB, F12, CRP, CFHR1, HABP2, and PPIA) critically involved in CVD–hematological disease pathway showed significant difference among groups. The PROS, F5, C5, FGG, and CFB levels associated with thrombosis and atherosclerosis induced by WD were significantly decreased by exercise intervention in WD EX. Furthermore, the F5 and FGG were well-demonstrated the important roles for thrombosis of atherosclerotic pathogenesis but the complement factor C5 in the development of atherosclerosis is not fully understood. In current study, the exercise could significantly alleviate the significantly elevated C5 and inflammation induced by WD group in accordance to amelioration of atherosclerosis. Therefore, exercise could mitigate chemotaxis through the modulation of the C5 level and innate immunity, thereby alle-viating the pathogenesis of atherosclerosis in western-diet induced obese mice.

Project description:In the present work endothelial function in the aorta and femoral artery assessed in vivo by magnetic resonance imaging (MRI) was characterized in male and female 8-, 14-, 22-, 28-, and 40-week-old E3L.CETP and C57BL/6J mice. Vascular nitric oxide (NO), eicosanoids and hydrogen peroxide (H2O2) production in the aorta, were measured by electron paramagnetic resonance spectroscopy (EPR), mass spectrometry (LC/MS) and fluoresence assay, respectively. Endothelial-specific protein plasma biomarkers and global alterations in plasma proteome were asssesed by targeted and non-targeted preotomics, respectively. In C57BL/6J endothelial dysfunction was observed in 40-week-old female and male mice as evidenced by impaired endothelium-dependent vasodilation induced by acetylcholine (Ach) in the aorta or by flow in the femoral artery (flow-mediated vasodilation, FMD). In E3L.CETP mice age-dependent endothelial dysfunction was accelerated and appeared in 14-22-week-old male and 22-28-week-old female mice. In 40 week-old E3L.CETP mice endothelial dysfunction was severe in both male and female mice and was more pronounced as compared with age-matched C57BL/6J mice. Despite severe endothelial dysfunction in 40 week-old mice E3L.CETP mice neither in the aortic roots nor in brachiocephalic artery atherosclerotic plaques were not detected. Interestingly, in the presence of NOS-inhibitor (L-NAME), FMD was inhibited in all experimental groups. However, effect of L-NAME on Ach–induced vasodilation in E3L.CETP mice, was blunted as compared with C57BL/6J mice, in particular in young E3L.CETP female mice. Furthermore, Ach–induced vasodilation in the aorta was inhibited by catalase, while H2O2 production was increased, in young female but not in male E3L.CETP mice. A switch from NO to H2O2-dependent vasodilation in young female E3L.CETP mice was associated with a blunted systemic inflammation and lower number of differentially expressed proteins (DEPs) in plasma than in young E3L.CETP male mice as compared with age-and sex-matched C57BL/6J mice. However, female and male 40-week-old E3L.CETP mice displayed similar number of DEPs in plasma vs respective sex-matched younger E3L.CETP mice. In the present work endothelial function in the aorta and femoral artery assessed in vivo by magnetic resonance imaging (MRI) was characterized in male and female 8-, 14-, 22-, 28-, and 40-week-old E3L.CETP and C57BL/6J mice. Vascular nitric oxide (NO), eicosanoids and hydrogen peroxide (H2O2) production in the aorta, were measured by electron paramagnetic resonance spectroscopy (EPR), mass spectrometry (LC/MS) and fluoresence assay, respectively. Endothelial-specific protein plasma biomarkers and global alterations in plasma proteome were asssesed by targeted and non-targeted preotomics, respectively. In C57BL/6J endothelial dysfunction was observed in 40-week-old female and male mice as evidenced by impaired endothelium-dependent vasodilation induced by acetylcholine (Ach) in the aorta or by flow in the femoral artery (flow-mediated vasodilation, FMD). In E3L.CETP mice age-dependent endothelial dysfunction was accelerated and appeared in 14-22-week-old male and 22-28-week-old female mice. In 40 week-old E3L.CETP mice endothelial dysfunction was severe in both male and female mice and was more pronounced as compared with age-matched C57BL/6J mice. Despite severe endothelial dysfunction in 40 week-old mice E3L.CETP mice neither in the aortic roots nor in brachiocephalic artery atherosclerotic plaques were not detected. Interestingly, in the presence of NOS-inhibitor (L-NAME), FMD was inhibited in all experimental groups. However, effect of L-NAME on Ach–induced vasodilation in E3L.CETP mice, was blunted as compared with C57BL/6J mice, in particular in young E3L.CETP female mice. Furthermore, Ach–induced vasodilation in the aorta was inhibited by catalase, while H2O2 production was increased, in young female but not in male E3L.CETP mice. A switch from NO to H2O2-dependent vasodilation in young female E3L.CETP mice was associated with a blunted systemic inflammation and lower number of differentially expressed proteins (DEPs) in plasma than in young E3L.CETP male mice as compared with age-and sex-matched C57BL/6J mice. However, female and male 40-week-old E3L.CETP mice displayed similar number of DEPs in plasma vs respective sex-matched younger E3L.CETP mice.

Dataset Information

The effect of opioid system inhibition on the Hmmr and Col1a1/ Col3a1 gene expression in relation to atherosclerotic plaque formation in aorta.

Dataset's files

Publications

Opioid System Antagonism Alters Vascular Proteome and Collagen Deposition in ApoE<sup>-/-</sup> Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

The effect of opioid system inhibition on the Hmmr and Col1a1/ Col3a1 gene expression in relation to atherosclerotic plaque formation in aorta.

Dataset's files

Publications

Opioid System Antagonism Alters Vascular Proteome and Collagen Deposition in ApoE&lt;sup&gt;-/-&lt;/sup&gt; Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Opioid System Antagonism Alters Vascular Proteome and Collagen Deposition in ApoE<sup>-/-</sup> Mice.