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GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential
Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hype...
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| Published in: | International journal of biological sciences 2021-01, Vol.17 (8), p.2050-2068 |
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| container_title | International journal of biological sciences |
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| creator | Ma, Xiaoxuan Liu, Zhenghong Ilyas, Iqra Little, Peter J Kamato, Danielle Sahebka, Amirhossein Chen, Zhengfang Luo, Sihui Zheng, Xueying Weng, Jianping Xu, Suowen |
| description | Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD. |
| doi_str_mv | 10.7150/ijbs.59965 |
| format | article |
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Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.</description><identifier>ISSN: 1449-2288</identifier><identifier>EISSN: 1449-2288</identifier><identifier>DOI: 10.7150/ijbs.59965</identifier><identifier>PMID: 34131405</identifier><language>eng</language><publisher>Australia: Ivyspring International Publisher Pty Ltd</publisher><subject>Agonists ; Angina pectoris ; Animal models ; Arteriosclerosis ; Atherosclerosis ; Atherosclerosis - drug therapy ; Atherosclerosis - metabolism ; Blood pressure ; Cardiomyocytes ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - metabolism ; Cardiovascular Diseases - prevention & control ; Cell culture ; Clinical trials ; Congestive heart failure ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; Disease prevention ; Drug therapy ; Endothelial cells ; Glucagon ; Glucagon-like peptide 1 ; Glucagon-Like Peptide-1 Receptor - agonists ; Glucagon-Like Peptide-1 Receptor - metabolism ; Glucose ; Hemoglobin ; Humans ; Hypertension ; Hypoglycemia ; Hypoglycemic Agents - pharmacology ; Inflammation ; Insulin ; Insulin secretion ; Ischemia ; Kinases ; Lipids ; Macrophages ; Molecular modelling ; Monocytes ; Mortality ; Muscles ; Proteins ; Receptors ; Review ; Risk factors ; Side effects ; Smooth muscle</subject><ispartof>International journal of biological sciences, 2021-01, Vol.17 (8), p.2050-2068</ispartof><rights>The author(s).</rights><rights>2021. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-7074f87549516fd59a3a2895f96d6a81224e3058222df40e7b103fd7fcb5bb773</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2598390568/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2598390568?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,730,783,787,888,25767,27938,27939,37026,37027,44604,53806,53808,75462</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34131405$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Xiaoxuan</creatorcontrib><creatorcontrib>Liu, Zhenghong</creatorcontrib><creatorcontrib>Ilyas, Iqra</creatorcontrib><creatorcontrib>Little, Peter J</creatorcontrib><creatorcontrib>Kamato, Danielle</creatorcontrib><creatorcontrib>Sahebka, Amirhossein</creatorcontrib><creatorcontrib>Chen, Zhengfang</creatorcontrib><creatorcontrib>Luo, Sihui</creatorcontrib><creatorcontrib>Zheng, Xueying</creatorcontrib><creatorcontrib>Weng, Jianping</creatorcontrib><creatorcontrib>Xu, Suowen</creatorcontrib><title>GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential</title><title>International journal of biological sciences</title><addtitle>Int J Biol Sci</addtitle><description>Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.</description><subject>Agonists</subject><subject>Angina pectoris</subject><subject>Animal models</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - drug therapy</subject><subject>Atherosclerosis - metabolism</subject><subject>Blood pressure</subject><subject>Cardiomyocytes</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - metabolism</subject><subject>Cardiovascular Diseases - prevention & control</subject><subject>Cell culture</subject><subject>Clinical trials</subject><subject>Congestive heart failure</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Disease prevention</subject><subject>Drug therapy</subject><subject>Endothelial cells</subject><subject>Glucagon</subject><subject>Glucagon-like peptide 1</subject><subject>Glucagon-Like Peptide-1 Receptor - agonists</subject><subject>Glucagon-Like Peptide-1 Receptor - metabolism</subject><subject>Glucose</subject><subject>Hemoglobin</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypoglycemia</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Inflammation</subject><subject>Insulin</subject><subject>Insulin secretion</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>Lipids</subject><subject>Macrophages</subject><subject>Molecular modelling</subject><subject>Monocytes</subject><subject>Mortality</subject><subject>Muscles</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Review</subject><subject>Risk factors</subject><subject>Side effects</subject><subject>Smooth muscle</subject><issn>1449-2288</issn><issn>1449-2288</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNpdkUtLxDAUhYMoPkY3_gApuFGhmmeTuBBEfMGAIuM6pGmqGTpNTVLBf29nRofR1b1wPs49lwPAIYLnHDF44aZlPGdSFmwD7CJKZY6xEJtr-w7Yi3EKISmYgNtgh1BEEIVsF0zux885yoI1tks-ZPrNty6mmJ0shJfreHqZGR0q5z91NH2jB8Yk59uY6bbK0rsNurN9cibrfLJtcrrZB1u1bqI9-Jkj8Hp3O7l5yMdP94831-PcUI5TziGnteCMSoaKumJSE42FZLUsqkILhDG1BDKBMa5qCi0vESR1xWtTsrLknIzA1dK368uZrcxwPehGdcHNdPhSXjv1V2ndu3rzn0ogSXBBB4OTH4PgP3obk5q5aGzT6Nb6PirMKOKiIHyOHv9Dp74P7fDeQElBJGSFGKizJWWCjzHYehUGQTUvS83LUouyBvhoPf4K_W2HfAOqjI8b</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Ma, Xiaoxuan</creator><creator>Liu, Zhenghong</creator><creator>Ilyas, Iqra</creator><creator>Little, Peter J</creator><creator>Kamato, Danielle</creator><creator>Sahebka, Amirhossein</creator><creator>Chen, Zhengfang</creator><creator>Luo, Sihui</creator><creator>Zheng, Xueying</creator><creator>Weng, Jianping</creator><creator>Xu, Suowen</creator><general>Ivyspring International Publisher Pty Ltd</general><general>Ivyspring International Publisher</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>7QL</scope><scope>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210101</creationdate><title>GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential</title><author>Ma, Xiaoxuan ; Liu, Zhenghong ; Ilyas, Iqra ; Little, Peter J ; Kamato, Danielle ; Sahebka, Amirhossein ; Chen, Zhengfang ; Luo, Sihui ; Zheng, Xueying ; Weng, Jianping ; Xu, Suowen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-7074f87549516fd59a3a2895f96d6a81224e3058222df40e7b103fd7fcb5bb773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Agonists</topic><topic>Angina pectoris</topic><topic>Animal models</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis - drug therapy</topic><topic>Atherosclerosis - metabolism</topic><topic>Blood pressure</topic><topic>Cardiomyocytes</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - metabolism</topic><topic>Cardiovascular Diseases - prevention & control</topic><topic>Cell culture</topic><topic>Clinical trials</topic><topic>Congestive heart failure</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Disease prevention</topic><topic>Drug therapy</topic><topic>Endothelial cells</topic><topic>Glucagon</topic><topic>Glucagon-like peptide 1</topic><topic>Glucagon-Like Peptide-1 Receptor - agonists</topic><topic>Glucagon-Like Peptide-1 Receptor - metabolism</topic><topic>Glucose</topic><topic>Hemoglobin</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypoglycemia</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Inflammation</topic><topic>Insulin</topic><topic>Insulin secretion</topic><topic>Ischemia</topic><topic>Kinases</topic><topic>Lipids</topic><topic>Macrophages</topic><topic>Molecular modelling</topic><topic>Monocytes</topic><topic>Mortality</topic><topic>Muscles</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Review</topic><topic>Risk factors</topic><topic>Side effects</topic><topic>Smooth muscle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Xiaoxuan</creatorcontrib><creatorcontrib>Liu, Zhenghong</creatorcontrib><creatorcontrib>Ilyas, Iqra</creatorcontrib><creatorcontrib>Little, Peter J</creatorcontrib><creatorcontrib>Kamato, Danielle</creatorcontrib><creatorcontrib>Sahebka, Amirhossein</creatorcontrib><creatorcontrib>Chen, Zhengfang</creatorcontrib><creatorcontrib>Luo, Sihui</creatorcontrib><creatorcontrib>Zheng, Xueying</creatorcontrib><creatorcontrib>Weng, Jianping</creatorcontrib><creatorcontrib>Xu, Suowen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</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 China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of biological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Xiaoxuan</au><au>Liu, Zhenghong</au><au>Ilyas, Iqra</au><au>Little, Peter J</au><au>Kamato, Danielle</au><au>Sahebka, Amirhossein</au><au>Chen, Zhengfang</au><au>Luo, Sihui</au><au>Zheng, Xueying</au><au>Weng, Jianping</au><au>Xu, Suowen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential</atitle><jtitle>International journal of biological sciences</jtitle><addtitle>Int J Biol Sci</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>17</volume><issue>8</issue><spage>2050</spage><epage>2068</epage><pages>2050-2068</pages><issn>1449-2288</issn><eissn>1449-2288</eissn><notes>ObjectType-Article-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-3</notes><notes>content type line 23</notes><notes>ObjectType-Review-1</notes><notes>Competing Interests: The authors have declared that no competing interest exists.</notes><abstract>Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>34131405</pmid><doi>10.7150/ijbs.59965</doi><tpages>19</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of biological sciences, 2021-01, Vol.17 (8), p.2050-2068 |
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| subjects | Agonists Angina pectoris Animal models Arteriosclerosis Atherosclerosis Atherosclerosis - drug therapy Atherosclerosis - metabolism Blood pressure Cardiomyocytes Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - metabolism Cardiovascular Diseases - prevention & control Cell culture Clinical trials Congestive heart failure Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Disease prevention Drug therapy Endothelial cells Glucagon Glucagon-like peptide 1 Glucagon-Like Peptide-1 Receptor - agonists Glucagon-Like Peptide-1 Receptor - metabolism Glucose Hemoglobin Humans Hypertension Hypoglycemia Hypoglycemic Agents - pharmacology Inflammation Insulin Insulin secretion Ischemia Kinases Lipids Macrophages Molecular modelling Monocytes Mortality Muscles Proteins Receptors Review Risk factors Side effects Smooth muscle |
| title | GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential |
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