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Abstract only
Heart failure impacts about 5.7 million people in the U.S. alone and the clinical signs often arise from changes in heart function. Cardiac hypertrophy is a known contributor to impaired cardiac contractility and ejection fraction. The heart deals with a working relationship with volume and pressure and thus mechanosensitive proteins may play a role on heart function. This study investigates the role of heparan sulfate proteoglycans, specifically syndecan1 (Sdc1) and glypican1 (Gpc1) on heart function and hypertrophy. We investigated if global deletion of Gpc1 and Sdc1 in mice alters heart histological features and thus cardiac function. Global male knockout mice for Sdc1 (Sdc1KO) and Gpc1 (Gpc1KO) were used and compared to its respective controls C57B6 and CD1 (7 weeks old). Left ventricular posterior wall thickness at end diastole (LVPWd), interventricular septal thickness at end of diastole (IVSTd) and left ventricular internal diameter in diastole (LVIDd) and myocyte cross‐sectional area in the left ventricle were assessed by transmission microscopy using hematoxylin & eosin (H&E) staining. Collagen deposition was assessed by Masson’s Trichrome staining. No differences in heart dimensions (LVPWd, IVSTd, LVIDd) were found between C57B6 and Sdc1KO. IVSTd and LVPWd was increased in Gpc1KO compared to CD1 (IVSTd: 1.15 mm for Gpc1KO and 1.03 mm for CD1; LVPWd: 0.75 mm for Gpc1KO and 0.64 mm for CD1). Both knock out lines showed decreased myocyte cross‐sectional area in the left ventricle size compared to its control (203.86 μm
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for Gpc1KO, 248.43 μm
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for CD1, 194.64 μm
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for Sdc1KO, and 239.02 μm
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for C57B6). Blind scoring of collagen staining showed that there was not a significant difference in collagen deposition between Gpc1KO and CD1 (1.14 for Gpc1KO and 0.99 for CD1). Taking together, these findings indicate that Sdc1KO and Gpc1KO show alterations in cardiac histological features. Our data raises the possibility of heparan sulfate proteoglycans being involved in cardiomyocyte proliferation or development. Particularly, Gpc1KO show the unique characteristic of having a hypertrophic heart without collagen deposition. Heparan sulfate proteoglycans may play a key role in cardiac function and we speculate that they may be involved in heart disease progression.
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Department of Anesthesiology, College of Medicine, University of Arizona, Tucson