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Ubiquinone oxidoreductase iron-sulfur protein 4 participates in vascular smooth muscle cell pyroptosis induced by Chlamydia pneumoniae infection through affecting mitochondrial function
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Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China)

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R363；R5

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    Abstract:

    Aim To explore the pyroptosis of vascular smooth muscle cell (VSMC) induced by Chlamydia pneumoniae (C.pn) infection and its possible mechanisms. Methods Primary rat VSMC were cultured by explant method. After the model of VSMC infected with C.pn was established, the changes in morphology of VSMC were observed under an inverted phase microscope, the lactic dehydrogenase (LDH) content was detected by the kit, and the expression levels of GSDMD and Caspase-1 were determined by Western blot, the changes in mitochondrial oxidative phosphorylation and the expression of complex-related proteins were measured by quantitative proteomic analysis by tandem mass tag technology and gene ontology. Results Compared with the control group, bubble-like vesicles were found outside the membrane of VSMC after C.pn infection under an inverted phase microscope. After C.pn infection of VSMC for 36 h and 48 h, LDH content increased by 38.92% and 79.54% (P＜0.001), respectively, and the expression of pyropotosis-related protein GSDMD increased by 1.74 times and 1.67 times (P＜0.001). After C.pn infection of VSMC for 48 h, the expression(pro-Caspase-1) and activity(Caspase-1 p12/p10)of Caspase-1 increased by 2.69 times and 3.47 times (P＜0.001), respectively. The mass spectrometry results showed that there were 20 differentially expressed proteins enriched in the oxidative phosphorylation pathway after C.pn infection, and at the same time, ComplexⅠubiquinone oxidoreductase iron-sulfur protein 4 (NDUFS4) decreased significantly. Further Western blot results showed that the expression level of NDUFS4 decreased by 57.5% and 57% (P＜0.001) after C.pn infection of VSMC for 36 h and 48 h respectively. Conclusion C.pn infection may induce VSMC pyroptosis by affecting mitochondrial function through downregulating NDUFS4 expression.

    Reference
    [1] ZHAO X, MIAO G L, ZHANG L J, et al.Chlamydia pneumoniae infection induces vascular smooth muscle cell migration and atherosclerosis through mitochondrial reactive oxygen species-mediated JunB-Fra-1 activation.Front Cell Dev Biol, 2,0:879023.
    [2] KALAYOGLU M V, LIBBY P, BYRNE G I.Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease.JAMA, 2,8(21):2724-2731.
    [3] DENISET J F, CHEUNG P K M, DIBROV E, et al.Chlamydophila pneumoniae infection leads to smooth muscle cell proliferation and thickening in the coronary artery without contributions from a host immune response.Am J Pathol, 0,6(2):1028-1037.
    [4] RDEL J, PROCHNAU D, PRAGER K, et al.Increased production of matrix metalloproteinases 1 and 3 by smooth muscle cells upon infection with Chlamydia pneumoniae.FEMS Immunol Med Microbiol, 3,8(2):159-164.
    [5] MA L, ZHANG L J, WANG B B, et al.Berberine inhibits Chlamydia pneumoniae infection-induced vascular smooth muscle cell migration through downregulating MMP3 and MMP9 via PI3K.Eur J Pharmacol, 5,5:102-109.
    [6] BAUMERT J, SCHMIDT K H, EITNER A, et al.Host cell cytokines induced by Chlamydia pneumoniae decrease the expression of interstitial collagens and fibronectin in fibroblasts.Infect Immun, 9,7(2):867-876.
    [7] LI Y Y, NIU X, XU H T, et al.VX-765 attenuates atherosclerosis in ApoE deficient mice by modulating VSMCs pyroptosis.Exp Cell Res, 0,9(1):111847.
    [8] TUMURKHUU G, DAGVADORJ J, PORRITT R A, et al.Chlamydia pneumoniae hijacks a host autoregulatory IL-1β loop to drive foam cell formation and accelerate atherosclerosis.Cell Metab, 8,8(3):432-448.e4.
    [9] MIAO G L, ZHAO X, CHAN S L, et al.Vascular smooth muscle cell c-Fos is critical for foam cell formation and atherosclerosis.Metabolism, 2,2:155213.
    [10] WANG B B, ZHANG L J, ZHANG T T, et al.Chlamydia pneumoniae infection promotes vascular smooth muscle cell migration through a Toll-like receptor 2-related signaling pathway.Infect Immun, 3,1(12):4583-4591.
    [11] CRAWFORD E D, WELLS J A.Caspase substrates and cellular remodeling.Annu Rev Biochem, 1,0:1055-1087.
    [12] LI W X, WEI D, LIANG J Y, et al.Comprehensive evaluation of white matter damage and neuron death and whole-transcriptome analysis of rats with chronic cerebral hypoperfusion.Front Cell Neurosci, 9,3:310.
    [13] ZHENG N B, ZHANG L J, WANG B B, et al.Chlamydia pneumoniae infection promotes vascular smooth muscle cell migration via c-Fos/interleukin-17C signaling.Int J Med Microbiol, 9,9(8):151340.
    [14] CHEN S, SHIMADA K N H, ZHANG W X, et al.IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae infection-accelerated atherosclerosis in mice.J Immunol, 0,5(9):5619-5627.
    [15] ERBEL C, DENGLER T J, WANGLER S, et al.Expression of IL-17A in human atherosclerotic lesions is associated with increased inflammation and plaque vulnerability.Basic Res Cardiol, 1,6(1):125-134.
    [16] PAN J Y, HAN L, GUO J, et al.AIM2 accelerates the atherosclerotic plaque progressions in ApoE－/－ mice.Biochem Biophys Res Commun, 8,8(3):487-494.
    [17] QIU Z, HE Y H, MING H, et al.Lipopolysaccharide (LPS) aggravates high glucose- and hypoxia/reoxygenation-induced injury through activating ROS-dependent NLRP3 inflammasome-mediated pyroptosis in H9c2 cardiomyocytes.J Diabetes Res, 9,9:8151836.
    [18] ALMEIDA-DA-SILVA C L C, ALPAGOT T, ZHU Y, et al.Chlamydia pneumoniae is present in the dental plaque of periodontitis patients and stimulates an inflammatory response in gingival epithelial cells.Microb Cell, 9,6(4):197-208.
    [19] SASU S, LAVERDA D, QURESHI N, et al.Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via Toll-like receptor 4 and p44/p42 mitogen-activated protein kinase activation.Circ Res, 1,9(3):244-250.
    [20] RIVERA J, WALDUCK A K, STRUGNELL R A, et al.Chlamydia pneumoniae induces a pro-inflammatory phenotype in murine vascular smooth muscle cells independently of elevating reactive oxygen species.Clin Exp Pharmacol Physiol, 2,9(3):218-226.
    [21] ZHU J, CHEN H, LE Y F, et al.Salvianolic acid A regulates pyroptosis of endothelial cells via directly targeting PKM2 and ameliorates diabetic atherosclerosis.Front Pharmacol, 2,3:1009229.
    [22] WU Z N, LIAO F, LUO G Q, et al.NR1D1 deletion induces rupture-prone vulnerable plaques by regulating macrophage pyroptosis via the NF- κ B/NLRP3 inflammasome pathway.Oxid Med Cell Longev, 2021.DOI:10.1155/2021/5217572.
    [23] 章舒蕾, 梁亚敏, 罗涔方, 等.琥珀酸通过活性氧途径诱导人脐静脉内皮细胞焦亡.中国动脉硬化杂志, 1,9(1):42-47.ZHANG S L, LIANG Y M, LUO C F, et al.Succinate induces pyroptosis of human umbilical vein endothelial cells via reactive oxygen species pathway.Chin J Arterioscler, 1,9(1):42-47.
    [24] KDING N, KAUFHOLD I, MLLER C, et al.Growth of Chlamydia pneumoniae is enhanced in cells with impaired mitochondrial function.Front Cell Infect Microbiol, 7,7:499.
    [25] NISR R B, AFFOURTIT C.Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation.Biochim Biophys Acta, 4,7(2):270-276.
    [26] KUZMIAK-GLANCY S, GLANCY B, KAY M W.Ischemic damage to every segment of the oxidative phosphorylation cascade elevates ETC driving force and ROS production in cardiac mitochondria.Am J Physiol Heart Circ Physiol, 2,3(3):H499-H512.
    [27] RODENBURG R J.Mitochondrial complex I-linked disease.Biochim Biophys Acta, 6,7(7):938-945.
    [28] SCACCO S, PETRUZZELLA V, BUDDE S, et al.Pathological mutations of the human NDUFS4 gene of the 18-kDa (AQDQ) subunit of complex I affect the expression of the protein and the assembly and function of the complex.J Biol Chem, 3,8(45):44161-44167.
    [29] STROUD D A, SURGENOR E E, FORMOSA L E, et al.Accessory subunits are integral for assembly and function of human mitochondrial complex I.Nature, 6,8(7623):123-126.
    [30] VALSECCHI F, GREFTE S, ROESTENBERG P, et al.Primary fibroblasts of NDUFS4－/－ mice display increased ROS levels and aberrant mitochondrial morphology.Mitochondrion, 3,3(5):436-443.
    [31] JIN Z X, WEI W, YANG M, et al.Mitochondrial complex I activity suppresses inflammation and enhances bone resorption by shifting macrophage-osteoclast polarization.Cell Metab, 4,0(3):483-498.
    [32] WEST A P.Mitochondrial dysfunction as a trigger of innate immune responses and inflammation.Toxicology, 7,1:54-63.
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ZHANG Yuke, ZHAO Xi, ZHANG Lijun, WANG Beibei, MIAO Guolin, ZHANG Qi, ZHANG Lijun. Ubiquinone oxidoreductase iron-sulfur protein 4 participates in vascular smooth muscle cell pyroptosis induced by Chlamydia pneumoniae infection through affecting mitochondrial function[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2023,31(7):573-580.

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  • Received:October 10,2022
  • Revised:January 24,2023
  • Online: September 01,2023
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