Dataset Information

Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction.

ABSTRACT:

Objective

Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction (HFpEF). MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-cause mortality in human studies. However, the role of MGP in arterial stiffness is uncertain. Approach and Results: We examined the association of ucMGP levels with vascular calcification, arterial stiffness including carotid-femoral pulse wave velocity (PWV), and incident heart failure in community-dwelling adults from the Framingham Heart Study. To further investigate the link between MGP and arterial stiffness, we compared aortic PWV in age- and sex-matched young (4-month-old) and aged (10-month-old) wild-type and Mgp^+/- mice. Among 7066 adults, we observed significant associations between higher levels of ucMGP and measures of arterial stiffness, including higher PWV and pulse pressure. Longitudinal analyses demonstrated an association between higher ucMGP levels and future increases in systolic blood pressure and incident HFpEF. Aortic PWV was increased in older, but not young, female Mgp^+/- mice compared with wild-type mice, and this augmentation in PWV was associated with increased aortic elastin fiber fragmentation and collagen accumulation.

Conclusions

This translational study demonstrates an association between ucMGP levels and arterial stiffness and future HFpEF in a large observational study, findings that are substantiated by experimental studies showing that mice with Mgp heterozygosity develop arterial stiffness. Taken together, these complementary study designs suggest a potential role of therapeutically targeting MGP in HFpEF.

SUBMITTER: Malhotra R

PROVIDER: S-EPMC8792238 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction.

Malhotra Rajeev R Nicholson Christopher J CJ Wang Dongyu D Bhambhani Vijeta V Paniagua Samantha S Slocum Charles C Sigurslid Haakon H HH Lino Cardenas Christian L CL Li Rebecca R Boerboom Sophie L SL Chen Yin-Ching YC Hwang Shih-Jen SJ Yao Chen C Ichinose Fumito F Bloch Donald B DB Lindsay Mark E ME Lewis Gregory D GD Aragam Jayashri R JR Hoffmann Udo U Mitchell Gary F GF Hamburg Naomi M NM Vasan Ramachandran S RS Benjamin Emelia J EJ Larson Martin G MG Zapol Warren M WM Cheng Susan S Roh Jason D JD O'Donnell Christopher J CJ Nguyen Christopher C Levy Daniel D Ho Jennifer E JE

Arteriosclerosis, thrombosis, and vascular biology 20211123 2

<h4>Objective</h4>Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction (HFpEF). MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-cause mortality in human studies. However, the role of MGP in arterial stiffness is uncertain. Approach and Results: We examined the as ...[more]

PMID: 34809448

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Dataset Information

Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction.

Objective

Conclusions

Publications

Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction.

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