Research progress of cathepsin B in cardiovascular diseases

doi:10.3877/cma.j.issn.2095-655X.2021.04.014

Abstract

Abstract:

Previous studies have shown that cathepsins are proteolytic enzymes that mediate protein hydrolysis in endosomes or lysosomes. Recently, accumulating studies have revealed that cathepsins also exist in the nucleus, cytoplasm, plasma membrane, and extracellular matrixes to mediate extracellular matrix protein degradation, signal transduction, and organelle protein processing and transport. Cathepsin B (CTSB) is one of the most abundant cathepsins in lysosomes, usually exists in the form of inactivated proenzyme, and has dual roles of endopeptidase and dipeptidase, which plays an important role in protein catabolism. In recent years, human studies and animal experiments have demonstrated that CTSB involves in many physiological and pathophysiological processes, such as extracellular matrix protein degradation, antigen presentation, and inflammatory body activation. These processes have been directly or indirectly implicated in the pathogenesis of cardiovascular diseases, including atherosclerosis, myocardial infarction and abdominal aortic aneurysm. And now, a large number of studies have found that SARS-CoV-2 enters host target cells through CTSB mediated pathway and leads to cell damage.The purpose of this review is to summarize the biological function of CTSB and related recent progress in cardiovascular diseases.

Key words: Cathepsin B, Cardiovascular disease, Atherosclerosis, Cardiomyopathy, dilated

Yu Zhou, Bo Yan. Research progress of cathepsin B in cardiovascular diseases[J]. Chinese Journal of Diagnostics(Electronic Edition), 2021, 09(04): 278-281.

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References 37

[1]	Liu CL, Guo JL, Zhang X, et al. Cysteine protease cathepsins in cardiovascular disease: from basic research to clinical trials[J]．Nat Rev Cardiol，2018，15(6)：351-370.
[2]	Mijanović O, Branković A, Panin AN，et al.Cathepsin B：a sellsword of cancer progression[J]．Cancer Lett，2019(449)：207-214.
[3]	Yadati T, Houben T, Bitorina A，et al.The ins and outs of cathepsins：physiological function and role in disease management[J]．Cells，2020，9(7)：1679.
[4]	Wang YP, Jia LL, Shen J，et al.Cathepsin B aggravates coxsackievirus B3-induced myocarditis through activating the inflammasome and promoting pyroptosis[J]．PLoS Pathog，2018，14(1)：e1006872.
[5]	Liu C, Cai ZL, Hu TT，et al.Cathepsin B aggravated doxorubicin-induced myocardial injury via NF-κB signalling[J]．Mol Med Rep，2020，22(6)：4848-4856.
[6]	Abdulla MH, Valli-Mohammed MA, Al-Khayal K，et al.Cathepsin B expression in colorectal cancer in a Middle East population: potential value as a tumor biomarker for late disease stages[J]．Oncol Rep，2017，37(6)：3175-3180.
[7]	Nishiga M, Wang DW, Han YL，et al.COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives[J]．Nat Rev Cardiol，2020，17(9)：543-558.
[8]	Padmanabhan P, Desikan R, Dixit NM.Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARS-CoV-2 infection[J]．PLoS Comput Biol，2020，16(12)：e1008461.
[9]	Yang J, Chen T, Zhou YF. Mediators of SARS-CoV-2 entry are preferentially enriched in cardiomyocytes[J]．Hereditas，2021，158(1)：4.
[10]	Hua Y, Nair S．Proteases in cardiometabolic diseases：pathophysiology，molecular mechanisms and clinical applications[J]．Biochim Biophys Acta，2015，1852(2)：195-208.
[11]	Gonçalves I, Hultman K, Dunér P，et al.High levels of cathepsin D and cystatin B are associated with increased risk of coronary events[J]．Open Heart，2016，3(1)：e000353.
[12]	Patel S, Homaei A, El-Seedi HR，et al.Cathepsins: proteases that are vital for survival but can also be fatal[J]．Biomed Pharmacother，2018(105)：526-532.
[13]	Bäck M, Yurdagul A Jr, Tabas I，et al.Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities[J]．Nat Rev Cardiol，2019，16(7)：389-406.
[14]	Zhang X, Luo S, Wang M，et al.Cysteinyl cathepsins in cardiovascular diseases[J]．Biochim Biophys Acta Proteins Proteom，2020，1868(4)：140360.
[15]	Chen J, Tung CH, Mahmood U，et al.In vivo imaging of proteolytic activity in atherosclerosis[J]．Circulation，2002，105(23)：2766-2771.
[16]	Savastano LE, Zhou Q, Smith A, et al. Multimodal laser-based angioscopy for structural，chemical and biological imaging of atherosclerosis[J]．Nat Biomed Eng，2017(1)：0023.
[17]	Wu H, Du Q, Dai Q，et al.Cysteine protease cathepsins in atherosclerotic cardiovascular diseases[J]．J Atheroscler Thromb，2018，25(2)：111-123.
[18]	Zhang GP, Yue X, Li SQ.Cathepsin C interacts with TNF-α/p38 MAPK signaling pathway to promote proliferation and metastasis in hepatocellular carcinoma[J]．Cancer Res Treat，2020，52(1)：10-23.
[19]	Zhang Y, Chen Y, Zhang YZ，et al.Contribution of cathepsin B-dependent Nlrp3 inflammasome activation to nicotine-induced endothelial barrier dysfunction[J]．Eur J Pharmacol，2019(865)：172795.
[20]	Vidak E, Javoršek U, Vizovišek M，et al.Cysteine cathepsins and their extracellular roles: shaping the microenvironment[J]．Cells，2019，8(3)：264.
[21]	Oshi M, Newman S, Tokumaru Y，et al.Intra-Tumoral angiogenesis is associated with inflammation，immune reaction and metastatic recurrence in breast cancer[J]．Int J Mol Sci，2020，21(18)：6708.
[22]	Zhang J, Shan Y, Li Y，et al.Palmitate impairs angiogenesis via suppression of cathepsin activity[J]．Mol Med Rep，2017，15(6)：3644-3650.
[23]	Im E, Venkatakrishnan A, Kazlauskas A．Cathepsin B regulates the intrinsic angiogenic threshold of endothelial cells[J]．Mol Biol Cell，2005，16(8)：3488-3500.
[24]	Nakao S, Zandi S, Sun D，et al.Cathepsin B-mediated CD18 shedding regulates leukocyte recruitment from angiogenic vessels[J]．FASEB J，2018，32(1)：143-154.
[25]	Thibeaux S, Siddiqi S, Zhelyabovska O，et al.Cathepsin B regulates hepatic lipid metabolism by cleaving liver fatty acid-binding protein[J]．J Biol Chem，2018，293(6)：1910-1923.
[26]	Dinnes DLM, White MY, Kockx M, et al. Human macrophage cathepsin B-mediated C-terminal cleavage of apolipoprotein A-I at Ser228 severely impairs antiatherogenic capacity[J]．FASEB J，2016，30(12)：4239-4255.
[27]	Sheedy FJ, Grebe A, Rayner KJ，et al.CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation[J]．Nat Immunol，2013，14(8)：812-820.
[28]	Thompson PL, Nidorf SM.Anti-inflammatory therapy with canakinumab for atherosclerotic disease：lessons from the CANTOS trial[J]．J Thorac Dis，2018，10(2)：695-698.
[29]	Wang YC, Liu XX, Shi H，et al.NLRP3 inflammasome，an immune-inflammatory target in pathogenesis and treatment of cardiovascular diseases[J]．Clin Transl Med，2020，10(1)：91-106.
[30]	Schultheiss HP, Fairweather D, Caforio ALP, et al. Dilated cardiomyopathy[J]．Nat Rev Dis Primers，2019，5(1)：32.
[31]	Liu L, Huang JJ, Liu Y，et al.Multiomics analysis of transcriptome，epigenome，and genome uncovers putative mechanisms for dilated cardiomyopathy[J]．Biomed Res Int，2021(2021)：6653802.
[32]	Wu QQ, Xu M, Yuan Y，et al.Cathepsin B deficiency attenuates cardiac remodeling in response to pressure overload via TNF-α/ASK1/JNK pathway[J]．Am J Physiol Heart Circ Physiol，2015，308(9)：1143-1154.
[33]	Lian D, Lai JQ, Wu YJ，et al.Cathepsin B-mediated NLRP3 inflammasome formation and activation in angiotensin Ⅱ-induced hypertensive mice: role of macrophage digestion dysfunction[J]．Cell Physiol Biochem，2018，50(4)：1585-1600.
[34]	Xie L, Terrand J, Xu B，et al.Cystatin C increases in cardiac injury：a role in extracellular matrix protein modulation[J]．Cardiovasc Res，2010，87(4)：628-635.
[35]	Camardo A, Carney S, Ramamurthi A．Assessing the targeting and fate of cathepsin k antibody-modified nanoparticles in a rat abdominal aortic aneurysm model[J]．Acta Biomater，2020(112)：225-233.
[36]	Yuan Z, Lu Y, Wei J，et al.Abdominal aortic aneurysm: roles of inflammatory cells[J]．Front Immunol，2020(11)：609161.
[37]	Lohoefer F, Reeps C, Lipp C，et al.Histopathological analysis of cellular localization of cathepsins in abdominal aortic aneurysm wall[J]．Int J Exp Pathol，2012，93(4)：252-258.

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