Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness
Advanced glycation end-products (AGEs) initiate cellular inflammation and contribute to cardiovascular disease in the elderly. AGE can be inhibited by Alagebrium (ALT), an AGE cross-link breaker. Moreover, the beneficial effects of exercise on aging are well recognized. Thus, we investigated the eff...
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| Veröffentlicht in: | Experimental gerontology 2012-08, Vol.47 (8), p.565-572 |
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| creator | Steppan, Jochen Tran, Huang Benjo, Alexandre M. Pellakuru, Laxsmi Barodka, Viachaslau Ryoo, Sungwoo Nyhan, Sineád M. Lussman, Craig Gupta, Gaurav White, Anthony R. Daher, Joao P. Shoukas, Artin A. Levine, Benjamin D. Berkowitz, Dan E. |
| description | Advanced glycation end-products (AGEs) initiate cellular inflammation and contribute to cardiovascular disease in the elderly. AGE can be inhibited by Alagebrium (ALT), an AGE cross-link breaker. Moreover, the beneficial effects of exercise on aging are well recognized. Thus, we investigated the effects of ALT and exercise (Ex) on cardiovascular function in a rat aging model. Compared to young (Y) rats, in sedentary old (O) rats, end-systolic elastance (Ees) decreased (0.9±0.2 vs 1.7±0.4mmHg/μL, P |
| doi_str_mv | 10.1016/j.exger.2012.04.006 |
| format | Article |
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► Aging decreases PWV, Ees, dP/dt, ventricular compliance and diastolic relaxation time. ► Exercise or an AGE-breaker alone ameliorate those effects. ► Combining exercise and an AGE-breaker improves those indices comparable to young animals.]]></description><identifier>ISSN: 0531-5565</identifier><identifier>EISSN: 1873-6815</identifier><identifier>DOI: 10.1016/j.exger.2012.04.006</identifier><identifier>PMID: 22569357</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Advanced glycation end-products ; AGE ; Aging - physiology ; Alagebrium ; Animals ; Diastole - physiology ; Drug Evaluation, Preclinical - methods ; Exercise ; Glycation End Products, Advanced - antagonists & inhibitors ; Glycation End Products, Advanced - metabolism ; Hemodynamics - physiology ; Male ; Physical Conditioning, Animal - physiology ; Rats ; Rats, Inbred F344 ; Systole - physiology ; Thiazoles - pharmacology ; Vascular Stiffness - drug effects ; Vascular Stiffness - physiology ; Ventricular Function, Left - drug effects ; Ventricular Function, Left - physiology ; Ventricular–vascular coupling</subject><ispartof>Experimental gerontology, 2012-08, Vol.47 (8), p.565-572</ispartof><rights>2012</rights><rights>Copyright © 2012. Published by Elsevier Inc.</rights><rights>2012 Published by Elsevier Inc. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-f04c78df06be41356c0f179baaba76bd21e70c30f8c164346d45f29143f474fb3</citedby><cites>FETCH-LOGICAL-c459t-f04c78df06be41356c0f179baaba76bd21e70c30f8c164346d45f29143f474fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0531556512000940$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22569357$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Steppan, Jochen</creatorcontrib><creatorcontrib>Tran, Huang</creatorcontrib><creatorcontrib>Benjo, Alexandre M.</creatorcontrib><creatorcontrib>Pellakuru, Laxsmi</creatorcontrib><creatorcontrib>Barodka, Viachaslau</creatorcontrib><creatorcontrib>Ryoo, Sungwoo</creatorcontrib><creatorcontrib>Nyhan, Sineád M.</creatorcontrib><creatorcontrib>Lussman, Craig</creatorcontrib><creatorcontrib>Gupta, Gaurav</creatorcontrib><creatorcontrib>White, Anthony R.</creatorcontrib><creatorcontrib>Daher, Joao P.</creatorcontrib><creatorcontrib>Shoukas, Artin A.</creatorcontrib><creatorcontrib>Levine, Benjamin D.</creatorcontrib><creatorcontrib>Berkowitz, Dan E.</creatorcontrib><title>Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness</title><title>Experimental gerontology</title><addtitle>Exp Gerontol</addtitle><description><![CDATA[Advanced glycation end-products (AGEs) initiate cellular inflammation and contribute to cardiovascular disease in the elderly. AGE can be inhibited by Alagebrium (ALT), an AGE cross-link breaker. Moreover, the beneficial effects of exercise on aging are well recognized. Thus, we investigated the effects of ALT and exercise (Ex) on cardiovascular function in a rat aging model. Compared to young (Y) rats, in sedentary old (O) rats, end-systolic elastance (Ees) decreased (0.9±0.2 vs 1.7±0.4mmHg/μL, P<0.05), dP/dtmax was attenuated (6054±685 vs 9540±939mmHg/s, P<0.05), ventricular compliance (end-diastolic pressure–volume relationship (EDPVR)) was impaired (1.4±0.2 vs 0.5±0.4mmHg/μL, P<0.05) and diastolic relaxation time (tau) was prolonged (21±3 vs 14±2ms, P<0.05). In old rats, combined ALT+Ex (4weeks) increased dP/dtmax and Ees (8945±665 vs 6054±685mmHg/s, and 1.5±0.2 vs 0.9±0.2 respectively, O with ALT+Ex vs O, P<0.05 for both). Diastolic function (exponential power of EDPVR and tau) was also substantially improved by treatment with Alt+Ex in old rats (0.4±0.1 vs 0.9±0.2 and 16±2 vs 21±3ms, respectively, O with ALT+EX vs O, P<0.05 for both). Pulse wave velocity (PWV) was increased in old rats (7.0±0.7 vs 3.8±0.3ms, O vs Y, P<0.01). Both ALT and Ex alone decreased PWV in old rats but the combination decreased PWV to levels observed in young (4.6±0.5 vs 3.8±0.3ms, O with ALT+Ex vs Y, NS). These results suggest that prevention of the formation of new AGEs (with exercise) and breakdown of already formed AGEs (with ALT) may represent a therapeutic strategy for age-related ventricular and vascular stiffness.
► Aging decreases PWV, Ees, dP/dt, ventricular compliance and diastolic relaxation time. ► Exercise or an AGE-breaker alone ameliorate those effects. ► Combining exercise and an AGE-breaker improves those indices comparable to young animals.]]></description><subject>Advanced glycation end-products</subject><subject>AGE</subject><subject>Aging - physiology</subject><subject>Alagebrium</subject><subject>Animals</subject><subject>Diastole - physiology</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Exercise</subject><subject>Glycation End Products, Advanced - antagonists & inhibitors</subject><subject>Glycation End Products, Advanced - metabolism</subject><subject>Hemodynamics - physiology</subject><subject>Male</subject><subject>Physical Conditioning, Animal - physiology</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Systole - physiology</subject><subject>Thiazoles - pharmacology</subject><subject>Vascular Stiffness - drug effects</subject><subject>Vascular Stiffness - physiology</subject><subject>Ventricular Function, Left - drug effects</subject><subject>Ventricular Function, Left - physiology</subject><subject>Ventricular–vascular coupling</subject><issn>0531-5565</issn><issn>1873-6815</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v1DAQxS1ERZfCJ0BCOXJJ8P8kB5CqCgpSpV7K2XKc8XZWiV3sZCnfHm-3VHDpyXry770ZzSPkHaMNo0x_3DVwv4XUcMp4Q2VDqX5BNqxrRa07pl6SDVWC1UppdUpe57yjheCCvSKnnCvdC9VuCJxPdgtDwnWuMFQuzgMGu2AM1S9cbiu4h-QwQ2VnmDAmu0CuiqO2OUeHRY7VHsKS0K2TTZUNRdt8FHlB7wPk_IaceDtlePv4npEfX7_cXHyrr64vv1-cX9VOqn6pPZWu7UZP9QCSCaUd9aztB2sH2-ph5Axa6gT1nWNaCqlHqTzvmRRettIP4ox8PubercMMozssZidzl3C26beJFs3_PwFvzTbujRSq111XAj48BqT4c4W8mBmzg2myAeKaDaNc8L5nfVtQcURdijkn8E9jGDWHgszOPBRkDgUZKk05f3G9_3fDJ8_fRgrw6QhAudMeiz07hOBgxARuMWPEZwf8AZRxplI</recordid><startdate>20120801</startdate><enddate>20120801</enddate><creator>Steppan, Jochen</creator><creator>Tran, Huang</creator><creator>Benjo, Alexandre M.</creator><creator>Pellakuru, Laxsmi</creator><creator>Barodka, Viachaslau</creator><creator>Ryoo, Sungwoo</creator><creator>Nyhan, Sineád M.</creator><creator>Lussman, Craig</creator><creator>Gupta, Gaurav</creator><creator>White, Anthony R.</creator><creator>Daher, Joao P.</creator><creator>Shoukas, Artin A.</creator><creator>Levine, Benjamin D.</creator><creator>Berkowitz, Dan E.</creator><general>Elsevier Inc</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120801</creationdate><title>Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness</title><author>Steppan, Jochen ; Tran, Huang ; Benjo, Alexandre M. ; Pellakuru, Laxsmi ; Barodka, Viachaslau ; Ryoo, Sungwoo ; Nyhan, Sineád M. ; Lussman, Craig ; Gupta, Gaurav ; White, Anthony R. ; Daher, Joao P. ; Shoukas, Artin A. ; Levine, Benjamin D. ; Berkowitz, Dan E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-f04c78df06be41356c0f179baaba76bd21e70c30f8c164346d45f29143f474fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Advanced glycation end-products</topic><topic>AGE</topic><topic>Aging - physiology</topic><topic>Alagebrium</topic><topic>Animals</topic><topic>Diastole - physiology</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Exercise</topic><topic>Glycation End Products, Advanced - antagonists & inhibitors</topic><topic>Glycation End Products, Advanced - metabolism</topic><topic>Hemodynamics - physiology</topic><topic>Male</topic><topic>Physical Conditioning, Animal - physiology</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Systole - physiology</topic><topic>Thiazoles - pharmacology</topic><topic>Vascular Stiffness - drug effects</topic><topic>Vascular Stiffness - physiology</topic><topic>Ventricular Function, Left - drug effects</topic><topic>Ventricular Function, Left - physiology</topic><topic>Ventricular–vascular coupling</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Steppan, Jochen</creatorcontrib><creatorcontrib>Tran, Huang</creatorcontrib><creatorcontrib>Benjo, Alexandre M.</creatorcontrib><creatorcontrib>Pellakuru, Laxsmi</creatorcontrib><creatorcontrib>Barodka, Viachaslau</creatorcontrib><creatorcontrib>Ryoo, Sungwoo</creatorcontrib><creatorcontrib>Nyhan, Sineád M.</creatorcontrib><creatorcontrib>Lussman, Craig</creatorcontrib><creatorcontrib>Gupta, Gaurav</creatorcontrib><creatorcontrib>White, Anthony R.</creatorcontrib><creatorcontrib>Daher, Joao P.</creatorcontrib><creatorcontrib>Shoukas, Artin A.</creatorcontrib><creatorcontrib>Levine, Benjamin D.</creatorcontrib><creatorcontrib>Berkowitz, Dan E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental gerontology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Steppan, Jochen</au><au>Tran, Huang</au><au>Benjo, Alexandre M.</au><au>Pellakuru, Laxsmi</au><au>Barodka, Viachaslau</au><au>Ryoo, Sungwoo</au><au>Nyhan, Sineád M.</au><au>Lussman, Craig</au><au>Gupta, Gaurav</au><au>White, Anthony R.</au><au>Daher, Joao P.</au><au>Shoukas, Artin A.</au><au>Levine, Benjamin D.</au><au>Berkowitz, Dan E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness</atitle><jtitle>Experimental gerontology</jtitle><addtitle>Exp Gerontol</addtitle><date>2012-08-01</date><risdate>2012</risdate><volume>47</volume><issue>8</issue><spage>565</spage><epage>572</epage><pages>565-572</pages><issn>0531-5565</issn><eissn>1873-6815</eissn><abstract><![CDATA[Advanced glycation end-products (AGEs) initiate cellular inflammation and contribute to cardiovascular disease in the elderly. AGE can be inhibited by Alagebrium (ALT), an AGE cross-link breaker. Moreover, the beneficial effects of exercise on aging are well recognized. Thus, we investigated the effects of ALT and exercise (Ex) on cardiovascular function in a rat aging model. Compared to young (Y) rats, in sedentary old (O) rats, end-systolic elastance (Ees) decreased (0.9±0.2 vs 1.7±0.4mmHg/μL, P<0.05), dP/dtmax was attenuated (6054±685 vs 9540±939mmHg/s, P<0.05), ventricular compliance (end-diastolic pressure–volume relationship (EDPVR)) was impaired (1.4±0.2 vs 0.5±0.4mmHg/μL, P<0.05) and diastolic relaxation time (tau) was prolonged (21±3 vs 14±2ms, P<0.05). In old rats, combined ALT+Ex (4weeks) increased dP/dtmax and Ees (8945±665 vs 6054±685mmHg/s, and 1.5±0.2 vs 0.9±0.2 respectively, O with ALT+Ex vs O, P<0.05 for both). Diastolic function (exponential power of EDPVR and tau) was also substantially improved by treatment with Alt+Ex in old rats (0.4±0.1 vs 0.9±0.2 and 16±2 vs 21±3ms, respectively, O with ALT+EX vs O, P<0.05 for both). Pulse wave velocity (PWV) was increased in old rats (7.0±0.7 vs 3.8±0.3ms, O vs Y, P<0.01). Both ALT and Ex alone decreased PWV in old rats but the combination decreased PWV to levels observed in young (4.6±0.5 vs 3.8±0.3ms, O with ALT+Ex vs Y, NS). These results suggest that prevention of the formation of new AGEs (with exercise) and breakdown of already formed AGEs (with ALT) may represent a therapeutic strategy for age-related ventricular and vascular stiffness.
► Aging decreases PWV, Ees, dP/dt, ventricular compliance and diastolic relaxation time. ► Exercise or an AGE-breaker alone ameliorate those effects. ► Combining exercise and an AGE-breaker improves those indices comparable to young animals.]]></abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>22569357</pmid><doi>10.1016/j.exger.2012.04.006</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Advanced glycation end-products AGE Aging - physiology Alagebrium Animals Diastole - physiology Drug Evaluation, Preclinical - methods Exercise Glycation End Products, Advanced - antagonists & inhibitors Glycation End Products, Advanced - metabolism Hemodynamics - physiology Male Physical Conditioning, Animal - physiology Rats Rats, Inbred F344 Systole - physiology Thiazoles - pharmacology Vascular Stiffness - drug effects Vascular Stiffness - physiology Ventricular Function, Left - drug effects Ventricular Function, Left - physiology Ventricular–vascular coupling |
| title | Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffness |
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