Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy
Dysregulated expression of lysosomal cysteine cathepsins is associated with adverse cardiac remodeling, a characteristic of several cardiovascular diseases. However, the information regarding the role of cysteine cathepsin L (CTSL) and cathepsin B (CTSB) in dilated cardiomyopathy (DCM) is limited. T...
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| Veröffentlicht in: | Molecular and cellular biochemistry 2017-04, Vol.428 (1-2), p.139-147 |
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| creator | Mehra, Siddharth Kumar, Manish Manchanda, Mansi Singh, Ratnakar Thakur, Bhaskar Rani, Neha Arava, Sudheer Narang, Rajiv Arya, Dharamvir Singh Chauhan, Shyam S. |
| description | Dysregulated expression of lysosomal cysteine cathepsins is associated with adverse cardiac remodeling, a characteristic of several cardiovascular diseases. However, the information regarding the role of cysteine cathepsin L (CTSL) and cathepsin B (CTSB) in dilated cardiomyopathy (DCM) is limited. The present study was aimed to investigate the expression of CTSL and CTSB in animal model of doxorubicin (doxo)-induced cardiomyopathy as well as in peripheral blood samples of DCM patients. Cardiac tissue sections from doxo-treated and control rats were used to study the expression of CTSL and CTSB by enzyme assay and immunohistochemistry (IHC). Peripheral blood mononuclear cells (PBMCs) isolated from DCM patients (
n
= 29) along with age-matched healthy controls (
n
= 28) were used to assay enzymatic activity of these cathepsins. Activities of these proteases were further correlated with echocardiographic parameters of DCM patients. A significant increase in CTSL activity and protein expression was observed with no changes in CTSB levels in doxo-treated rats as compared to controls. We also observed a drastic increase in the functional activity of cathepsin L+cathepsin B (CTSL+B), CTSL, and CTSB in DCM patients compared to controls (
p
≤ 0.001). Increased levels of these proteases exhibited a statistically significant correlation with reduced left ventricular ejection fraction (LVEF) in DCM patients (
ρ
= −0.58,
p
= 0.01). For the first time, this study demonstrates a correlation between increased expression of CTSL and CTSB in PBMCs with severity of left ventricular dysfunction in DCM patients. Thus, these proteases may serve as blood-based biomarker of DCM and prove useful in its management. |
| doi_str_mv | 10.1007/s11010-016-2924-6 |
| format | Article |
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n
= 29) along with age-matched healthy controls (
n
= 28) were used to assay enzymatic activity of these cathepsins. Activities of these proteases were further correlated with echocardiographic parameters of DCM patients. A significant increase in CTSL activity and protein expression was observed with no changes in CTSB levels in doxo-treated rats as compared to controls. We also observed a drastic increase in the functional activity of cathepsin L+cathepsin B (CTSL+B), CTSL, and CTSB in DCM patients compared to controls (
p
≤ 0.001). Increased levels of these proteases exhibited a statistically significant correlation with reduced left ventricular ejection fraction (LVEF) in DCM patients (
ρ
= −0.58,
p
= 0.01). For the first time, this study demonstrates a correlation between increased expression of CTSL and CTSB in PBMCs with severity of left ventricular dysfunction in DCM patients. Thus, these proteases may serve as blood-based biomarker of DCM and prove useful in its management.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-016-2924-6</identifier><identifier>PMID: 28074340</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Animal models ; Animals ; Anthracyclines ; Biochemistry ; Biomarkers ; Biomarkers - blood ; Biomedical and Life Sciences ; Cardiology ; Cardiomyopathy ; Cardiomyopathy, Dilated - chemically induced ; Cardiomyopathy, Dilated - metabolism ; Cardiomyopathy, Dilated - physiopathology ; Cardiovascular diseases ; Cathepsin B - blood ; Cathepsin L - blood ; Cathepsins ; Congestive cardiomyopathy ; Cysteine ; Disease Models, Animal ; Doxorubicin - adverse effects ; Echocardiography ; Enzymatic activity ; Enzymes ; Female ; Heart Ventricles - physiopathology ; Humans ; Immunohistochemistry ; Life Sciences ; Male ; Medical Biochemistry ; Middle Aged ; Oncology ; Protein expression ; Rats ; Stroke Volume ; Up-Regulation</subject><ispartof>Molecular and cellular biochemistry, 2017-04, Vol.428 (1-2), p.139-147</ispartof><rights>Springer Science+Business Media New York 2017</rights><rights>COPYRIGHT 2017 Springer</rights><rights>Molecular and Cellular Biochemistry is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-ddffc096e6220cd6cb9b355f54f2674e7090c11266d3732e7eaf8778eb3f4fc73</citedby><cites>FETCH-LOGICAL-c472t-ddffc096e6220cd6cb9b355f54f2674e7090c11266d3732e7eaf8778eb3f4fc73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11010-016-2924-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11010-016-2924-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28074340$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mehra, Siddharth</creatorcontrib><creatorcontrib>Kumar, Manish</creatorcontrib><creatorcontrib>Manchanda, Mansi</creatorcontrib><creatorcontrib>Singh, Ratnakar</creatorcontrib><creatorcontrib>Thakur, Bhaskar</creatorcontrib><creatorcontrib>Rani, Neha</creatorcontrib><creatorcontrib>Arava, Sudheer</creatorcontrib><creatorcontrib>Narang, Rajiv</creatorcontrib><creatorcontrib>Arya, Dharamvir Singh</creatorcontrib><creatorcontrib>Chauhan, Shyam S.</creatorcontrib><title>Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><addtitle>Mol Cell Biochem</addtitle><description>Dysregulated expression of lysosomal cysteine cathepsins is associated with adverse cardiac remodeling, a characteristic of several cardiovascular diseases. However, the information regarding the role of cysteine cathepsin L (CTSL) and cathepsin B (CTSB) in dilated cardiomyopathy (DCM) is limited. The present study was aimed to investigate the expression of CTSL and CTSB in animal model of doxorubicin (doxo)-induced cardiomyopathy as well as in peripheral blood samples of DCM patients. Cardiac tissue sections from doxo-treated and control rats were used to study the expression of CTSL and CTSB by enzyme assay and immunohistochemistry (IHC). Peripheral blood mononuclear cells (PBMCs) isolated from DCM patients (
n
= 29) along with age-matched healthy controls (
n
= 28) were used to assay enzymatic activity of these cathepsins. Activities of these proteases were further correlated with echocardiographic parameters of DCM patients. A significant increase in CTSL activity and protein expression was observed with no changes in CTSB levels in doxo-treated rats as compared to controls. We also observed a drastic increase in the functional activity of cathepsin L+cathepsin B (CTSL+B), CTSL, and CTSB in DCM patients compared to controls (
p
≤ 0.001). Increased levels of these proteases exhibited a statistically significant correlation with reduced left ventricular ejection fraction (LVEF) in DCM patients (
ρ
= −0.58,
p
= 0.01). For the first time, this study demonstrates a correlation between increased expression of CTSL and CTSB in PBMCs with severity of left ventricular dysfunction in DCM patients. Thus, these proteases may serve as blood-based biomarker of DCM and prove useful in its management.</description><subject>Adult</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anthracyclines</subject><subject>Biochemistry</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Biomedical and Life Sciences</subject><subject>Cardiology</subject><subject>Cardiomyopathy</subject><subject>Cardiomyopathy, Dilated - chemically induced</subject><subject>Cardiomyopathy, Dilated - metabolism</subject><subject>Cardiomyopathy, Dilated - physiopathology</subject><subject>Cardiovascular diseases</subject><subject>Cathepsin B - blood</subject><subject>Cathepsin L - blood</subject><subject>Cathepsins</subject><subject>Congestive cardiomyopathy</subject><subject>Cysteine</subject><subject>Disease Models, Animal</subject><subject>Doxorubicin - adverse effects</subject><subject>Echocardiography</subject><subject>Enzymatic activity</subject><subject>Enzymes</subject><subject>Female</subject><subject>Heart Ventricles - physiopathology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medical Biochemistry</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Protein expression</subject><subject>Rats</subject><subject>Stroke Volume</subject><subject>Up-Regulation</subject><issn>0300-8177</issn><issn>1573-4919</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkUuLFDEUhYMoTjv6A9xIgRs3Nd68K8ux8QXNzGZch3QebYaqpE2qF_3vTdGjtKIwBPK49zuXHA5CrzFcYQD5vmIMGHrAoieKsF48QSvMJe2ZwuopWgEF6Acs5QV6Ues9NBgwfo4uyACSUQYrdLMeY4rWjF2NuxRDuybruxw6a-bvfl9j6jadSe7s_aFrm4ujmf1SLi7m6Zj3rX98iZ4FM1b_6uG8RN8-fbxbf-k3t5-_rq83vWWSzL1zIVhQwgtCwDpht2pLOQ-cBSIk8xIUWIyJEI5KSrz0JgxSDn5LAwtW0kv07jR3X_KPg6-znmK1fhxN8vlQNR6abaa4egzKpeSUw9DQt3-h9_lQUjPSKMlFI_EZtTOj1zGFPBdjl6H6mnNQTA1SNOrqH1Rbzk_R5uRDbPU_BPgksCXXWnzQ-xInU44ag17i1qe4dYtbL3HrRfPm4cOH7eTdb8WvfBtATkBtrbTz5czRf6f-BIEHsc0</recordid><startdate>20170401</startdate><enddate>20170401</enddate><creator>Mehra, Siddharth</creator><creator>Kumar, Manish</creator><creator>Manchanda, Mansi</creator><creator>Singh, Ratnakar</creator><creator>Thakur, Bhaskar</creator><creator>Rani, Neha</creator><creator>Arava, Sudheer</creator><creator>Narang, Rajiv</creator><creator>Arya, Dharamvir Singh</creator><creator>Chauhan, Shyam S.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20170401</creationdate><title>Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy</title><author>Mehra, Siddharth ; Kumar, Manish ; Manchanda, Mansi ; Singh, Ratnakar ; Thakur, Bhaskar ; Rani, Neha ; Arava, Sudheer ; Narang, Rajiv ; Arya, Dharamvir Singh ; Chauhan, Shyam S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-ddffc096e6220cd6cb9b355f54f2674e7090c11266d3732e7eaf8778eb3f4fc73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anthracyclines</topic><topic>Biochemistry</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Biomedical and Life Sciences</topic><topic>Cardiology</topic><topic>Cardiomyopathy</topic><topic>Cardiomyopathy, Dilated - chemically induced</topic><topic>Cardiomyopathy, Dilated - metabolism</topic><topic>Cardiomyopathy, Dilated - physiopathology</topic><topic>Cardiovascular diseases</topic><topic>Cathepsin B - blood</topic><topic>Cathepsin L - blood</topic><topic>Cathepsins</topic><topic>Congestive cardiomyopathy</topic><topic>Cysteine</topic><topic>Disease Models, Animal</topic><topic>Doxorubicin - adverse effects</topic><topic>Echocardiography</topic><topic>Enzymatic activity</topic><topic>Enzymes</topic><topic>Female</topic><topic>Heart Ventricles - physiopathology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Medical Biochemistry</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Protein expression</topic><topic>Rats</topic><topic>Stroke Volume</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mehra, Siddharth</creatorcontrib><creatorcontrib>Kumar, Manish</creatorcontrib><creatorcontrib>Manchanda, Mansi</creatorcontrib><creatorcontrib>Singh, Ratnakar</creatorcontrib><creatorcontrib>Thakur, Bhaskar</creatorcontrib><creatorcontrib>Rani, Neha</creatorcontrib><creatorcontrib>Arava, Sudheer</creatorcontrib><creatorcontrib>Narang, Rajiv</creatorcontrib><creatorcontrib>Arya, Dharamvir Singh</creatorcontrib><creatorcontrib>Chauhan, Shyam S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mehra, Siddharth</au><au>Kumar, Manish</au><au>Manchanda, Mansi</au><au>Singh, Ratnakar</au><au>Thakur, Bhaskar</au><au>Rani, Neha</au><au>Arava, Sudheer</au><au>Narang, Rajiv</au><au>Arya, Dharamvir Singh</au><au>Chauhan, Shyam S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy</atitle><jtitle>Molecular and cellular biochemistry</jtitle><stitle>Mol Cell Biochem</stitle><addtitle>Mol Cell Biochem</addtitle><date>2017-04-01</date><risdate>2017</risdate><volume>428</volume><issue>1-2</issue><spage>139</spage><epage>147</epage><pages>139-147</pages><issn>0300-8177</issn><eissn>1573-4919</eissn><abstract>Dysregulated expression of lysosomal cysteine cathepsins is associated with adverse cardiac remodeling, a characteristic of several cardiovascular diseases. However, the information regarding the role of cysteine cathepsin L (CTSL) and cathepsin B (CTSB) in dilated cardiomyopathy (DCM) is limited. The present study was aimed to investigate the expression of CTSL and CTSB in animal model of doxorubicin (doxo)-induced cardiomyopathy as well as in peripheral blood samples of DCM patients. Cardiac tissue sections from doxo-treated and control rats were used to study the expression of CTSL and CTSB by enzyme assay and immunohistochemistry (IHC). Peripheral blood mononuclear cells (PBMCs) isolated from DCM patients (
n
= 29) along with age-matched healthy controls (
n
= 28) were used to assay enzymatic activity of these cathepsins. Activities of these proteases were further correlated with echocardiographic parameters of DCM patients. A significant increase in CTSL activity and protein expression was observed with no changes in CTSB levels in doxo-treated rats as compared to controls. We also observed a drastic increase in the functional activity of cathepsin L+cathepsin B (CTSL+B), CTSL, and CTSB in DCM patients compared to controls (
p
≤ 0.001). Increased levels of these proteases exhibited a statistically significant correlation with reduced left ventricular ejection fraction (LVEF) in DCM patients (
ρ
= −0.58,
p
= 0.01). For the first time, this study demonstrates a correlation between increased expression of CTSL and CTSB in PBMCs with severity of left ventricular dysfunction in DCM patients. Thus, these proteases may serve as blood-based biomarker of DCM and prove useful in its management.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28074340</pmid><doi>10.1007/s11010-016-2924-6</doi><tpages>9</tpages></addata></record> |
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| ispartof | Molecular and cellular biochemistry, 2017-04, Vol.428 (1-2), p.139-147 |
| issn | 0300-8177 1573-4919 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adult Animal models Animals Anthracyclines Biochemistry Biomarkers Biomarkers - blood Biomedical and Life Sciences Cardiology Cardiomyopathy Cardiomyopathy, Dilated - chemically induced Cardiomyopathy, Dilated - metabolism Cardiomyopathy, Dilated - physiopathology Cardiovascular diseases Cathepsin B - blood Cathepsin L - blood Cathepsins Congestive cardiomyopathy Cysteine Disease Models, Animal Doxorubicin - adverse effects Echocardiography Enzymatic activity Enzymes Female Heart Ventricles - physiopathology Humans Immunohistochemistry Life Sciences Male Medical Biochemistry Middle Aged Oncology Protein expression Rats Stroke Volume Up-Regulation |
| title | Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy |
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