Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice
Objective: Cytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix with contractile filaments. During abdominal aortic aneurysm (AAA) development, (1) aortic medial degeneration is associated with loss of smooth muscle cell integrity and (2) fibrogenic me...
Gespeichert in:
| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2021-05, Vol.41 (5), p.1694-1709 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1709 |
|---|---|
| container_issue | 5 |
| container_start_page | 1694 |
| container_title | Arteriosclerosis, thrombosis, and vascular biology |
| container_volume | 41 |
| creator | Muniappan, Latha Okuyama, Michihiro Javidan, Aida Thiagarajan, Devi Jiang, Weihua Moorleghen, Jessica J. Yang, Lihua Balakrishnan, Anju Howatt, Deborah A. Uchida, Haruhito A. Saido, Takaomi C. Subramanian, Venkateswaran |
| description | Objective:
Cytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix with contractile filaments. During abdominal aortic aneurysm (AAA) development, (1) aortic medial degeneration is associated with loss of smooth muscle cell integrity and (2) fibrogenic mesenchymal cells mediate extracellular matrix remodeling. Calpains cleave cytoskeletal proteins that maintain cell structural integrity. Pharmacological inhibition of calpains exert beneficial effects on Ang II (angiotensin II)-induced AAAs in LDLR-/- (low-density receptor deficient) mice. Here, we evaluated the functional contribution of fibrogenic mesenchymal cells-derived calpain-2 on (1) cytoskeletal structural protein and extracellular matrix alterations and (2) AAA progression.
Approach and Results:
Calpain-2 protein and cytoskeletal protein (filamin and talin) fragmentation are significantly elevated in human and Ang II-induced AAAs in mice. To examine the relative contribution of calpain-2 in AAA development, calpain-2 floxed mice in an LDLR-/- background were bred to mice with a tamoxifen-inducible form of Cre under control of either the ubiquitous promoter, chicken beta-actin, or fibrogenic mesenchymal cell-specific promoter, Col1 alpha 2 (collagen type 1 alpha 2). Ubiquitous or fibrogenic mesenchymal cell-specific depletion of calpain-2 in mice suppressed Ang II-induced AAAs, filamin/talin fragmentation, while promoting extracellular matrix protein, collagen in the aortas. Calpain-2 silencing in aortic smooth muscle cells or fibroblasts reduced Ang II-induced filamin fragmentation. In addition, silencing of filamin in aortic SMCs significantly reduced collagen protein. Furthermore, calpain-2 deficiency suppressed rupture of established Ang II-induced AAAs in mice.
Conclusions:
Our studies implicate that calpain-2 deficiency prevents (1) Ang II-induced cytoskeletal structural protein fragmentation and AAA development and (2) stabilize and suppress rupture of established AAAs in mice. |
| doi_str_mv | 10.1161/ATVBAHA.120.315546 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_webof</sourceid><recordid>TN_cdi_webofscience_primary_000642642400014</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>33761765</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4471-bf2e8b61e4d3ced3fc2c01199e5487bd6e75ac0e5b14310be620be0594546b433</originalsourceid><addsrcrecordid>eNqNkc1uEzEUhS0EoiXwAizQ7NEE_0-yQRoGaCsFsSlsLdtzpzE4dmR7WvXtcZQ0gh2yZV_J5zvWPRehtwQvCZHkQ3_781N_3S8JxUtGhODyGbokgvKWSyaf1xp361ZITi_Qq5x_YYw5pfglumCsk6ST4hJtbsI4W2c8NJ9h76G4GJo4NYP2e-1CS5tvrrg7XSA3vRnjzgXtmz6m4mzTB5jTY941LlSZhdfoxaR9hjene4F-fP1yO1y3m-9XN0O_aS3nHWnNRGFlJAE-Mgsjmyy1mJD1GgRfdWaU0AltMQhDOCPYgKT1wGLNa4uGM7ZAH4---9nsYLQQStJe7ZPb6fSoonbq35fgtuou3qsVlpThrhrQo4FNMecE05klWB2yVadsVc1WHbOt0Lu_fz0jT2FWwfuj4AFMnLJ1ECycZTX9Oom6ea1qYwu0-n_14Io-jGaIcygV5Sc0-gIp__bzAyS1Be3L9oByJrFoKaYEi7ragwdhfwB5j6YO</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice</title><source>MEDLINE</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><source>Alma/SFX Local Collection</source><creator>Muniappan, Latha ; Okuyama, Michihiro ; Javidan, Aida ; Thiagarajan, Devi ; Jiang, Weihua ; Moorleghen, Jessica J. ; Yang, Lihua ; Balakrishnan, Anju ; Howatt, Deborah A. ; Uchida, Haruhito A. ; Saido, Takaomi C. ; Subramanian, Venkateswaran</creator><creatorcontrib>Muniappan, Latha ; Okuyama, Michihiro ; Javidan, Aida ; Thiagarajan, Devi ; Jiang, Weihua ; Moorleghen, Jessica J. ; Yang, Lihua ; Balakrishnan, Anju ; Howatt, Deborah A. ; Uchida, Haruhito A. ; Saido, Takaomi C. ; Subramanian, Venkateswaran</creatorcontrib><description>Objective:
Cytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix with contractile filaments. During abdominal aortic aneurysm (AAA) development, (1) aortic medial degeneration is associated with loss of smooth muscle cell integrity and (2) fibrogenic mesenchymal cells mediate extracellular matrix remodeling. Calpains cleave cytoskeletal proteins that maintain cell structural integrity. Pharmacological inhibition of calpains exert beneficial effects on Ang II (angiotensin II)-induced AAAs in LDLR-/- (low-density receptor deficient) mice. Here, we evaluated the functional contribution of fibrogenic mesenchymal cells-derived calpain-2 on (1) cytoskeletal structural protein and extracellular matrix alterations and (2) AAA progression.
Approach and Results:
Calpain-2 protein and cytoskeletal protein (filamin and talin) fragmentation are significantly elevated in human and Ang II-induced AAAs in mice. To examine the relative contribution of calpain-2 in AAA development, calpain-2 floxed mice in an LDLR-/- background were bred to mice with a tamoxifen-inducible form of Cre under control of either the ubiquitous promoter, chicken beta-actin, or fibrogenic mesenchymal cell-specific promoter, Col1 alpha 2 (collagen type 1 alpha 2). Ubiquitous or fibrogenic mesenchymal cell-specific depletion of calpain-2 in mice suppressed Ang II-induced AAAs, filamin/talin fragmentation, while promoting extracellular matrix protein, collagen in the aortas. Calpain-2 silencing in aortic smooth muscle cells or fibroblasts reduced Ang II-induced filamin fragmentation. In addition, silencing of filamin in aortic SMCs significantly reduced collagen protein. Furthermore, calpain-2 deficiency suppressed rupture of established Ang II-induced AAAs in mice.
Conclusions:
Our studies implicate that calpain-2 deficiency prevents (1) Ang II-induced cytoskeletal structural protein fragmentation and AAA development and (2) stabilize and suppress rupture of established AAAs in mice.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.120.315546</identifier><identifier>PMID: 33761765</identifier><language>eng</language><publisher>PHILADELPHIA: Lippincott Williams & Wilkins</publisher><subject>Aged ; Aged, 80 and over ; Angiotensin II ; Animals ; Aorta, Abdominal - enzymology ; Aorta, Abdominal - pathology ; Aortic Aneurysm, Abdominal - chemically induced ; Aortic Aneurysm, Abdominal - enzymology ; Aortic Aneurysm, Abdominal - genetics ; Aortic Aneurysm, Abdominal - prevention & control ; Aortic Rupture - chemically induced ; Aortic Rupture - enzymology ; Aortic Rupture - genetics ; Aortic Rupture - prevention & control ; Calpain - deficiency ; Calpain - genetics ; Calpain - metabolism ; Cardiovascular System & Cardiology ; Cells, Cultured ; Cytoskeleton - enzymology ; Cytoskeleton - pathology ; Dilatation, Pathologic ; Disease Models, Animal ; Extracellular Matrix - enzymology ; Extracellular Matrix - pathology ; Female ; Hematology ; Humans ; Life Sciences & Biomedicine ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Peripheral Vascular Disease ; Rats ; Receptors, LDL - deficiency ; Receptors, LDL - genetics ; Science & Technology ; Vascular Remodeling</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2021-05, Vol.41 (5), p.1694-1709</ispartof><rights>Lippincott Williams & Wilkins</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>4</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000642642400014</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c4471-bf2e8b61e4d3ced3fc2c01199e5487bd6e75ac0e5b14310be620be0594546b433</citedby><cites>FETCH-LOGICAL-c4471-bf2e8b61e4d3ced3fc2c01199e5487bd6e75ac0e5b14310be620be0594546b433</cites><orcidid>0000-0002-1183-7717</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930,39263</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33761765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Muniappan, Latha</creatorcontrib><creatorcontrib>Okuyama, Michihiro</creatorcontrib><creatorcontrib>Javidan, Aida</creatorcontrib><creatorcontrib>Thiagarajan, Devi</creatorcontrib><creatorcontrib>Jiang, Weihua</creatorcontrib><creatorcontrib>Moorleghen, Jessica J.</creatorcontrib><creatorcontrib>Yang, Lihua</creatorcontrib><creatorcontrib>Balakrishnan, Anju</creatorcontrib><creatorcontrib>Howatt, Deborah A.</creatorcontrib><creatorcontrib>Uchida, Haruhito A.</creatorcontrib><creatorcontrib>Saido, Takaomi C.</creatorcontrib><creatorcontrib>Subramanian, Venkateswaran</creatorcontrib><title>Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>ARTERIOSCL THROM VAS</addtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>Objective:
Cytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix with contractile filaments. During abdominal aortic aneurysm (AAA) development, (1) aortic medial degeneration is associated with loss of smooth muscle cell integrity and (2) fibrogenic mesenchymal cells mediate extracellular matrix remodeling. Calpains cleave cytoskeletal proteins that maintain cell structural integrity. Pharmacological inhibition of calpains exert beneficial effects on Ang II (angiotensin II)-induced AAAs in LDLR-/- (low-density receptor deficient) mice. Here, we evaluated the functional contribution of fibrogenic mesenchymal cells-derived calpain-2 on (1) cytoskeletal structural protein and extracellular matrix alterations and (2) AAA progression.
Approach and Results:
Calpain-2 protein and cytoskeletal protein (filamin and talin) fragmentation are significantly elevated in human and Ang II-induced AAAs in mice. To examine the relative contribution of calpain-2 in AAA development, calpain-2 floxed mice in an LDLR-/- background were bred to mice with a tamoxifen-inducible form of Cre under control of either the ubiquitous promoter, chicken beta-actin, or fibrogenic mesenchymal cell-specific promoter, Col1 alpha 2 (collagen type 1 alpha 2). Ubiquitous or fibrogenic mesenchymal cell-specific depletion of calpain-2 in mice suppressed Ang II-induced AAAs, filamin/talin fragmentation, while promoting extracellular matrix protein, collagen in the aortas. Calpain-2 silencing in aortic smooth muscle cells or fibroblasts reduced Ang II-induced filamin fragmentation. In addition, silencing of filamin in aortic SMCs significantly reduced collagen protein. Furthermore, calpain-2 deficiency suppressed rupture of established Ang II-induced AAAs in mice.
Conclusions:
Our studies implicate that calpain-2 deficiency prevents (1) Ang II-induced cytoskeletal structural protein fragmentation and AAA development and (2) stabilize and suppress rupture of established AAAs in mice.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angiotensin II</subject><subject>Animals</subject><subject>Aorta, Abdominal - enzymology</subject><subject>Aorta, Abdominal - pathology</subject><subject>Aortic Aneurysm, Abdominal - chemically induced</subject><subject>Aortic Aneurysm, Abdominal - enzymology</subject><subject>Aortic Aneurysm, Abdominal - genetics</subject><subject>Aortic Aneurysm, Abdominal - prevention & control</subject><subject>Aortic Rupture - chemically induced</subject><subject>Aortic Rupture - enzymology</subject><subject>Aortic Rupture - genetics</subject><subject>Aortic Rupture - prevention & control</subject><subject>Calpain - deficiency</subject><subject>Calpain - genetics</subject><subject>Calpain - metabolism</subject><subject>Cardiovascular System & Cardiology</subject><subject>Cells, Cultured</subject><subject>Cytoskeleton - enzymology</subject><subject>Cytoskeleton - pathology</subject><subject>Dilatation, Pathologic</subject><subject>Disease Models, Animal</subject><subject>Extracellular Matrix - enzymology</subject><subject>Extracellular Matrix - pathology</subject><subject>Female</subject><subject>Hematology</subject><subject>Humans</subject><subject>Life Sciences & Biomedicine</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Middle Aged</subject><subject>Peripheral Vascular Disease</subject><subject>Rats</subject><subject>Receptors, LDL - deficiency</subject><subject>Receptors, LDL - genetics</subject><subject>Science & Technology</subject><subject>Vascular Remodeling</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqNkc1uEzEUhS0EoiXwAizQ7NEE_0-yQRoGaCsFsSlsLdtzpzE4dmR7WvXtcZQ0gh2yZV_J5zvWPRehtwQvCZHkQ3_781N_3S8JxUtGhODyGbokgvKWSyaf1xp361ZITi_Qq5x_YYw5pfglumCsk6ST4hJtbsI4W2c8NJ9h76G4GJo4NYP2e-1CS5tvrrg7XSA3vRnjzgXtmz6m4mzTB5jTY941LlSZhdfoxaR9hjene4F-fP1yO1y3m-9XN0O_aS3nHWnNRGFlJAE-Mgsjmyy1mJD1GgRfdWaU0AltMQhDOCPYgKT1wGLNa4uGM7ZAH4---9nsYLQQStJe7ZPb6fSoonbq35fgtuou3qsVlpThrhrQo4FNMecE05klWB2yVadsVc1WHbOt0Lu_fz0jT2FWwfuj4AFMnLJ1ECycZTX9Oom6ea1qYwu0-n_14Io-jGaIcygV5Sc0-gIp__bzAyS1Be3L9oByJrFoKaYEi7ragwdhfwB5j6YO</recordid><startdate>20210505</startdate><enddate>20210505</enddate><creator>Muniappan, Latha</creator><creator>Okuyama, Michihiro</creator><creator>Javidan, Aida</creator><creator>Thiagarajan, Devi</creator><creator>Jiang, Weihua</creator><creator>Moorleghen, Jessica J.</creator><creator>Yang, Lihua</creator><creator>Balakrishnan, Anju</creator><creator>Howatt, Deborah A.</creator><creator>Uchida, Haruhito A.</creator><creator>Saido, Takaomi C.</creator><creator>Subramanian, Venkateswaran</creator><general>Lippincott Williams & Wilkins</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><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>5PM</scope><orcidid>https://orcid.org/0000-0002-1183-7717</orcidid></search><sort><creationdate>20210505</creationdate><title>Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice</title><author>Muniappan, Latha ; Okuyama, Michihiro ; Javidan, Aida ; Thiagarajan, Devi ; Jiang, Weihua ; Moorleghen, Jessica J. ; Yang, Lihua ; Balakrishnan, Anju ; Howatt, Deborah A. ; Uchida, Haruhito A. ; Saido, Takaomi C. ; Subramanian, Venkateswaran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4471-bf2e8b61e4d3ced3fc2c01199e5487bd6e75ac0e5b14310be620be0594546b433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angiotensin II</topic><topic>Animals</topic><topic>Aorta, Abdominal - enzymology</topic><topic>Aorta, Abdominal - pathology</topic><topic>Aortic Aneurysm, Abdominal - chemically induced</topic><topic>Aortic Aneurysm, Abdominal - enzymology</topic><topic>Aortic Aneurysm, Abdominal - genetics</topic><topic>Aortic Aneurysm, Abdominal - prevention & control</topic><topic>Aortic Rupture - chemically induced</topic><topic>Aortic Rupture - enzymology</topic><topic>Aortic Rupture - genetics</topic><topic>Aortic Rupture - prevention & control</topic><topic>Calpain - deficiency</topic><topic>Calpain - genetics</topic><topic>Calpain - metabolism</topic><topic>Cardiovascular System & Cardiology</topic><topic>Cells, Cultured</topic><topic>Cytoskeleton - enzymology</topic><topic>Cytoskeleton - pathology</topic><topic>Dilatation, Pathologic</topic><topic>Disease Models, Animal</topic><topic>Extracellular Matrix - enzymology</topic><topic>Extracellular Matrix - pathology</topic><topic>Female</topic><topic>Hematology</topic><topic>Humans</topic><topic>Life Sciences & Biomedicine</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Middle Aged</topic><topic>Peripheral Vascular Disease</topic><topic>Rats</topic><topic>Receptors, LDL - deficiency</topic><topic>Receptors, LDL - genetics</topic><topic>Science & Technology</topic><topic>Vascular Remodeling</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muniappan, Latha</creatorcontrib><creatorcontrib>Okuyama, Michihiro</creatorcontrib><creatorcontrib>Javidan, Aida</creatorcontrib><creatorcontrib>Thiagarajan, Devi</creatorcontrib><creatorcontrib>Jiang, Weihua</creatorcontrib><creatorcontrib>Moorleghen, Jessica J.</creatorcontrib><creatorcontrib>Yang, Lihua</creatorcontrib><creatorcontrib>Balakrishnan, Anju</creatorcontrib><creatorcontrib>Howatt, Deborah A.</creatorcontrib><creatorcontrib>Uchida, Haruhito A.</creatorcontrib><creatorcontrib>Saido, Takaomi C.</creatorcontrib><creatorcontrib>Subramanian, Venkateswaran</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muniappan, Latha</au><au>Okuyama, Michihiro</au><au>Javidan, Aida</au><au>Thiagarajan, Devi</au><au>Jiang, Weihua</au><au>Moorleghen, Jessica J.</au><au>Yang, Lihua</au><au>Balakrishnan, Anju</au><au>Howatt, Deborah A.</au><au>Uchida, Haruhito A.</au><au>Saido, Takaomi C.</au><au>Subramanian, Venkateswaran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><stitle>ARTERIOSCL THROM VAS</stitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2021-05-05</date><risdate>2021</risdate><volume>41</volume><issue>5</issue><spage>1694</spage><epage>1709</epage><pages>1694-1709</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><abstract>Objective:
Cytoskeletal structural proteins maintain cell structural integrity by bridging extracellular matrix with contractile filaments. During abdominal aortic aneurysm (AAA) development, (1) aortic medial degeneration is associated with loss of smooth muscle cell integrity and (2) fibrogenic mesenchymal cells mediate extracellular matrix remodeling. Calpains cleave cytoskeletal proteins that maintain cell structural integrity. Pharmacological inhibition of calpains exert beneficial effects on Ang II (angiotensin II)-induced AAAs in LDLR-/- (low-density receptor deficient) mice. Here, we evaluated the functional contribution of fibrogenic mesenchymal cells-derived calpain-2 on (1) cytoskeletal structural protein and extracellular matrix alterations and (2) AAA progression.
Approach and Results:
Calpain-2 protein and cytoskeletal protein (filamin and talin) fragmentation are significantly elevated in human and Ang II-induced AAAs in mice. To examine the relative contribution of calpain-2 in AAA development, calpain-2 floxed mice in an LDLR-/- background were bred to mice with a tamoxifen-inducible form of Cre under control of either the ubiquitous promoter, chicken beta-actin, or fibrogenic mesenchymal cell-specific promoter, Col1 alpha 2 (collagen type 1 alpha 2). Ubiquitous or fibrogenic mesenchymal cell-specific depletion of calpain-2 in mice suppressed Ang II-induced AAAs, filamin/talin fragmentation, while promoting extracellular matrix protein, collagen in the aortas. Calpain-2 silencing in aortic smooth muscle cells or fibroblasts reduced Ang II-induced filamin fragmentation. In addition, silencing of filamin in aortic SMCs significantly reduced collagen protein. Furthermore, calpain-2 deficiency suppressed rupture of established Ang II-induced AAAs in mice.
Conclusions:
Our studies implicate that calpain-2 deficiency prevents (1) Ang II-induced cytoskeletal structural protein fragmentation and AAA development and (2) stabilize and suppress rupture of established AAAs in mice.</abstract><cop>PHILADELPHIA</cop><pub>Lippincott Williams & Wilkins</pub><pmid>33761765</pmid><doi>10.1161/ATVBAHA.120.315546</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-1183-7717</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1079-5642 |
| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2021-05, Vol.41 (5), p.1694-1709 |
| issn | 1079-5642 1524-4636 |
| language | eng |
| recordid | cdi_webofscience_primary_000642642400014 |
| source | MEDLINE; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Alma/SFX Local Collection |
| subjects | Aged Aged, 80 and over Angiotensin II Animals Aorta, Abdominal - enzymology Aorta, Abdominal - pathology Aortic Aneurysm, Abdominal - chemically induced Aortic Aneurysm, Abdominal - enzymology Aortic Aneurysm, Abdominal - genetics Aortic Aneurysm, Abdominal - prevention & control Aortic Rupture - chemically induced Aortic Rupture - enzymology Aortic Rupture - genetics Aortic Rupture - prevention & control Calpain - deficiency Calpain - genetics Calpain - metabolism Cardiovascular System & Cardiology Cells, Cultured Cytoskeleton - enzymology Cytoskeleton - pathology Dilatation, Pathologic Disease Models, Animal Extracellular Matrix - enzymology Extracellular Matrix - pathology Female Hematology Humans Life Sciences & Biomedicine Male Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Peripheral Vascular Disease Rats Receptors, LDL - deficiency Receptors, LDL - genetics Science & Technology Vascular Remodeling |
| title | Inducible Depletion of Calpain-2 Mitigates Abdominal Aortic Aneurysm in Mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T03%3A46%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_webof&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inducible%20Depletion%20of%20Calpain-2%20Mitigates%20Abdominal%20Aortic%20Aneurysm%20in%20Mice&rft.jtitle=Arteriosclerosis,%20thrombosis,%20and%20vascular%20biology&rft.au=Muniappan,%20Latha&rft.date=2021-05-05&rft.volume=41&rft.issue=5&rft.spage=1694&rft.epage=1709&rft.pages=1694-1709&rft.issn=1079-5642&rft.eissn=1524-4636&rft_id=info:doi/10.1161/ATVBAHA.120.315546&rft_dat=%3Cpubmed_webof%3E33761765%3C/pubmed_webof%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/33761765&rfr_iscdi=true |