Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus
Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protei...
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| Veröffentlicht in: | American journal of hypertension 2017-02, Vol.30 (2), p.196-201 |
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| creator | Sardana, Mayank Vasim, Izzah Varakantam, Swapna Kewan, Uzma Tariq, Ali Koppula, Maheshwara R Syed, Amer Ahmed Beraun, Melissa Drummen, Nadja E A Vermeer, Cees Akers, Scott R Chirinos, Julio A |
| description | Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes.
We enrolled a multiethnic cohort of 66 participants with type 2 diabetes. Carotid-femoral pulse wave velocity (CF-PWV) was measured with high-fidelity arterial tonometry (Sphygmocor Device). Dp-ucMGP was measured with ELISA (VitaK; The Netherlands).
The majority of the participants were middle-aged (62 ± 12 years), male (91%), and had a history of hypertension (82%). Average hemoglobin A1C was 7.2% (55 mmol/mol). Mean dp-ucMGP was 624 ± 638 pmol/l and mean CF-PWV was 11 ± 4 m/sec. In multivariable analyses, dp-ucMGP was independently related to African American ethnicity (β = -0.24, P = 0.005), warfarin use (β = 0.56, P < 0.001), and estimated glomerular filtration rate (eGFR, β = -0.32, P < 0.001). Dp-ucMGP predicted CF-PWV (β = 0.40, P = 0.011), even after adjustment for age, gender, ethnicity, mean arterial pressure, eGFR, and warfarin use.
In our cross-sectional analysis, circulating dp-ucMGP was independently associated with CF-PWV in type 2 diabetes. This suggests that deficient vitamin K-dependent activation of MGP may lead to large artery stiffening and could be targeted with vitamin K supplementation in the patients with diabetes. |
| doi_str_mv | 10.1093/ajh/hpw146 |
| format | Article |
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We enrolled a multiethnic cohort of 66 participants with type 2 diabetes. Carotid-femoral pulse wave velocity (CF-PWV) was measured with high-fidelity arterial tonometry (Sphygmocor Device). Dp-ucMGP was measured with ELISA (VitaK; The Netherlands).
The majority of the participants were middle-aged (62 ± 12 years), male (91%), and had a history of hypertension (82%). Average hemoglobin A1C was 7.2% (55 mmol/mol). Mean dp-ucMGP was 624 ± 638 pmol/l and mean CF-PWV was 11 ± 4 m/sec. In multivariable analyses, dp-ucMGP was independently related to African American ethnicity (β = -0.24, P = 0.005), warfarin use (β = 0.56, P < 0.001), and estimated glomerular filtration rate (eGFR, β = -0.32, P < 0.001). Dp-ucMGP predicted CF-PWV (β = 0.40, P = 0.011), even after adjustment for age, gender, ethnicity, mean arterial pressure, eGFR, and warfarin use.
In our cross-sectional analysis, circulating dp-ucMGP was independently associated with CF-PWV in type 2 diabetes. This suggests that deficient vitamin K-dependent activation of MGP may lead to large artery stiffening and could be targeted with vitamin K supplementation in the patients with diabetes.</description><identifier>ISSN: 0895-7061</identifier><identifier>EISSN: 1941-7225</identifier><identifier>DOI: 10.1093/ajh/hpw146</identifier><identifier>PMID: 27927630</identifier><language>eng</language><publisher>United States</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers - blood ; Calcium-Binding Proteins - blood ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - physiopathology ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix Proteins - blood ; Female ; Humans ; Incidence ; Male ; Matrix Gla Protein ; Middle Aged ; Pulse Wave Analysis ; United States - epidemiology ; Vascular Calcification - blood ; Vascular Calcification - epidemiology ; Vascular Calcification - etiology ; Vascular Stiffness - physiology ; Young Adult</subject><ispartof>American journal of hypertension, 2017-02, Vol.30 (2), p.196-201</ispartof><rights>American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c323t-1c4f31114b0e30444d3ad2538b28d2a806ac63a8d8058bfb1b22628662ba2da33</citedby><cites>FETCH-LOGICAL-c323t-1c4f31114b0e30444d3ad2538b28d2a806ac63a8d8058bfb1b22628662ba2da33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27927630$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sardana, Mayank</creatorcontrib><creatorcontrib>Vasim, Izzah</creatorcontrib><creatorcontrib>Varakantam, Swapna</creatorcontrib><creatorcontrib>Kewan, Uzma</creatorcontrib><creatorcontrib>Tariq, Ali</creatorcontrib><creatorcontrib>Koppula, Maheshwara R</creatorcontrib><creatorcontrib>Syed, Amer Ahmed</creatorcontrib><creatorcontrib>Beraun, Melissa</creatorcontrib><creatorcontrib>Drummen, Nadja E A</creatorcontrib><creatorcontrib>Vermeer, Cees</creatorcontrib><creatorcontrib>Akers, Scott R</creatorcontrib><creatorcontrib>Chirinos, Julio A</creatorcontrib><title>Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus</title><title>American journal of hypertension</title><addtitle>Am J Hypertens</addtitle><description>Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes.
We enrolled a multiethnic cohort of 66 participants with type 2 diabetes. Carotid-femoral pulse wave velocity (CF-PWV) was measured with high-fidelity arterial tonometry (Sphygmocor Device). Dp-ucMGP was measured with ELISA (VitaK; The Netherlands).
The majority of the participants were middle-aged (62 ± 12 years), male (91%), and had a history of hypertension (82%). Average hemoglobin A1C was 7.2% (55 mmol/mol). Mean dp-ucMGP was 624 ± 638 pmol/l and mean CF-PWV was 11 ± 4 m/sec. In multivariable analyses, dp-ucMGP was independently related to African American ethnicity (β = -0.24, P = 0.005), warfarin use (β = 0.56, P < 0.001), and estimated glomerular filtration rate (eGFR, β = -0.32, P < 0.001). Dp-ucMGP predicted CF-PWV (β = 0.40, P = 0.011), even after adjustment for age, gender, ethnicity, mean arterial pressure, eGFR, and warfarin use.
In our cross-sectional analysis, circulating dp-ucMGP was independently associated with CF-PWV in type 2 diabetes. This suggests that deficient vitamin K-dependent activation of MGP may lead to large artery stiffening and could be targeted with vitamin K supplementation in the patients with diabetes.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers - blood</subject><subject>Calcium-Binding Proteins - blood</subject><subject>Cross-Sectional Studies</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Extracellular Matrix Proteins - blood</subject><subject>Female</subject><subject>Humans</subject><subject>Incidence</subject><subject>Male</subject><subject>Matrix Gla Protein</subject><subject>Middle Aged</subject><subject>Pulse Wave Analysis</subject><subject>United States - epidemiology</subject><subject>Vascular Calcification - blood</subject><subject>Vascular Calcification - epidemiology</subject><subject>Vascular Calcification - etiology</subject><subject>Vascular Stiffness - physiology</subject><subject>Young Adult</subject><issn>0895-7061</issn><issn>1941-7225</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kF1LwzAYhYMobk5v_AGSSxHq8tU0vRybzsGmgvO6vGlTltG1NUnV_Xsrm16di_NwODwIXVNyT0nKx7DdjDftFxXyBA1pKmiUMBafoiFRaRwlRNIBuvB-SwgRUtJzNGBJyhLJyRA9L2rIg_00eAXB2W88ryB6dU0wtsZQF3jignEWKvwWbFnWxnvcN-t9azDDMwvaBOPxylSVDZ2_RGclVN5cHXOE3h8f1tOnaPkyX0wnyyjnjIeI5qLklFKhieFECFFwKFjMlWaqYKCIhFxyUIUisdKlppoxyZSUTAMrgPMRuj3stq756IwP2c76vD8BtWk6n1ElEpWkCSU9endAc9d470yZtc7uwO0zSrJff1nvLzv46-Gb426nd6b4R_-E8R-KW2r4</recordid><startdate>201702</startdate><enddate>201702</enddate><creator>Sardana, Mayank</creator><creator>Vasim, Izzah</creator><creator>Varakantam, Swapna</creator><creator>Kewan, Uzma</creator><creator>Tariq, Ali</creator><creator>Koppula, Maheshwara R</creator><creator>Syed, Amer Ahmed</creator><creator>Beraun, Melissa</creator><creator>Drummen, Nadja E A</creator><creator>Vermeer, Cees</creator><creator>Akers, Scott R</creator><creator>Chirinos, Julio A</creator><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></search><sort><creationdate>201702</creationdate><title>Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus</title><author>Sardana, Mayank ; Vasim, Izzah ; Varakantam, Swapna ; Kewan, Uzma ; Tariq, Ali ; Koppula, Maheshwara R ; Syed, Amer Ahmed ; Beraun, Melissa ; Drummen, Nadja E A ; Vermeer, Cees ; Akers, Scott R ; Chirinos, Julio A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c323t-1c4f31114b0e30444d3ad2538b28d2a806ac63a8d8058bfb1b22628662ba2da33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers - blood</topic><topic>Calcium-Binding Proteins - blood</topic><topic>Cross-Sectional Studies</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Extracellular Matrix Proteins - blood</topic><topic>Female</topic><topic>Humans</topic><topic>Incidence</topic><topic>Male</topic><topic>Matrix Gla Protein</topic><topic>Middle Aged</topic><topic>Pulse Wave Analysis</topic><topic>United States - epidemiology</topic><topic>Vascular Calcification - blood</topic><topic>Vascular Calcification - epidemiology</topic><topic>Vascular Calcification - etiology</topic><topic>Vascular Stiffness - physiology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sardana, Mayank</creatorcontrib><creatorcontrib>Vasim, Izzah</creatorcontrib><creatorcontrib>Varakantam, Swapna</creatorcontrib><creatorcontrib>Kewan, Uzma</creatorcontrib><creatorcontrib>Tariq, Ali</creatorcontrib><creatorcontrib>Koppula, Maheshwara R</creatorcontrib><creatorcontrib>Syed, Amer Ahmed</creatorcontrib><creatorcontrib>Beraun, Melissa</creatorcontrib><creatorcontrib>Drummen, Nadja E A</creatorcontrib><creatorcontrib>Vermeer, Cees</creatorcontrib><creatorcontrib>Akers, Scott R</creatorcontrib><creatorcontrib>Chirinos, Julio A</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><jtitle>American journal of hypertension</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sardana, Mayank</au><au>Vasim, Izzah</au><au>Varakantam, Swapna</au><au>Kewan, Uzma</au><au>Tariq, Ali</au><au>Koppula, Maheshwara R</au><au>Syed, Amer Ahmed</au><au>Beraun, Melissa</au><au>Drummen, Nadja E A</au><au>Vermeer, Cees</au><au>Akers, Scott R</au><au>Chirinos, Julio A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus</atitle><jtitle>American journal of hypertension</jtitle><addtitle>Am J Hypertens</addtitle><date>2017-02</date><risdate>2017</risdate><volume>30</volume><issue>2</issue><spage>196</spage><epage>201</epage><pages>196-201</pages><issn>0895-7061</issn><eissn>1941-7225</eissn><abstract>Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes.
We enrolled a multiethnic cohort of 66 participants with type 2 diabetes. Carotid-femoral pulse wave velocity (CF-PWV) was measured with high-fidelity arterial tonometry (Sphygmocor Device). Dp-ucMGP was measured with ELISA (VitaK; The Netherlands).
The majority of the participants were middle-aged (62 ± 12 years), male (91%), and had a history of hypertension (82%). Average hemoglobin A1C was 7.2% (55 mmol/mol). Mean dp-ucMGP was 624 ± 638 pmol/l and mean CF-PWV was 11 ± 4 m/sec. In multivariable analyses, dp-ucMGP was independently related to African American ethnicity (β = -0.24, P = 0.005), warfarin use (β = 0.56, P < 0.001), and estimated glomerular filtration rate (eGFR, β = -0.32, P < 0.001). Dp-ucMGP predicted CF-PWV (β = 0.40, P = 0.011), even after adjustment for age, gender, ethnicity, mean arterial pressure, eGFR, and warfarin use.
In our cross-sectional analysis, circulating dp-ucMGP was independently associated with CF-PWV in type 2 diabetes. This suggests that deficient vitamin K-dependent activation of MGP may lead to large artery stiffening and could be targeted with vitamin K supplementation in the patients with diabetes.</abstract><cop>United States</cop><pmid>27927630</pmid><doi>10.1093/ajh/hpw146</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Aged, 80 and over Biomarkers - blood Calcium-Binding Proteins - blood Cross-Sectional Studies Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - physiopathology Enzyme-Linked Immunosorbent Assay Extracellular Matrix Proteins - blood Female Humans Incidence Male Matrix Gla Protein Middle Aged Pulse Wave Analysis United States - epidemiology Vascular Calcification - blood Vascular Calcification - epidemiology Vascular Calcification - etiology Vascular Stiffness - physiology Young Adult |
| title | Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus |
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