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Updated: Aug 11, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Growth hormone-releasing hormone agonist attenuates vascular calcification in diabetic db/db mice
Hao-Lin Ren1, Ruiping Cai2,3, Ruize Xue2,3
1Department of Radiology, The First Affiliated Hospital, Dalian Medical University, Dalian, China.
Introduction:
Vascular calcification (VC) is an independent risk factor for cardiovascular diseases. VC increases mortality of all-causes. VC is one of most common cardiovascular complications in type II diabetes. So far, no therapy has been proven to be effective in treatment of clinical VC. The present study investigated the therapeutic effects of MR409, an agonistic analog of growth hormone-releasing hormone (GHRH-A), on VC in diabetic db/db mice.
Method And Result:
Diabetic mice were injected with MR409 subcutaneously every day for 8 weeks. Long-term treatment with MR409 improved serum lipid profile and endothelium-dependent relaxation to acetylcholine, and reduced vascular structural injury in diabetic mice without affecting serum growth hormone level. Echocardiography showed that calcium plaques present in heart valve of diabetic mice disappeared in diabetic mice after treatment with MR409. MR409 inhibited vascular calcium deposition associated with a marked reduction in the expressions of osteogenic-regulated alkaline phosphatase (ALP) and transcription osteogenic marker gene Runx2 in diabetic mice. MR409 also inhibited vascular reactive oxygen species (ROS) generation and upregulated the expressions of anti-calcifying protein Klotho in diabetic mice.
Discussion:
Our results demonstrate that GHRH-A MR409 can effectively attenuate VC and heart valve calcification, and protect against endothelial dysfunction and vascular injury in diabetic mice without significantly affecting pituitary-growth hormone axis. The mechanisms may involve upregulation of anti-calcifying protein Klotho and reduction in vascular ROS and the expression of redox sensitive osteogenic genes Runx2 and ALP. GHRH-A may represent a new pharmacological strategy for treatment of VC and diabetics associated cardiovascular complications.
Insights
Growth hormone-releasing hormone analog MR409 effectively treats vascular calcification in diabetic mice. This therapy reduces arterial and heart valve calcification, improving cardiovascular health by upregulating Klotho and reducing oxidative stress.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Pharmacology
Background:
- Vascular calcification (VC) is a significant risk factor for cardiovascular diseases and mortality, particularly in type II diabetes.
- Current therapeutic options for clinical VC are limited, highlighting the need for novel treatment strategies.
Purpose of the Study:
- To investigate the therapeutic potential of MR409, a growth hormone-releasing hormone analog (GHRH-A), in treating vascular calcification in a mouse model of type II diabetes.
Main Methods:
- Diabetic db/db mice received daily subcutaneous injections of MR409 for 8 weeks.
- Evaluated effects on serum lipid profile, endothelial function, vascular structure, and calcification markers.
- Assessed changes in osteogenic gene expression (ALP, Runx2), reactive oxygen species (ROS), and Klotho protein levels.
Main Results:
- MR409 treatment improved lipid profiles, endothelial function, and reduced vascular injury in diabetic mice.
- Significant reduction in vascular and heart valve calcification was observed.
- MR409 inhibited vascular calcium deposition by downregulating osteogenic markers (ALP, Runx2) and reducing ROS, while upregulating the anti-calcifying protein Klotho.
Conclusions:
- GHRH-A MR409 demonstrates significant efficacy in attenuating vascular calcification and heart valve calcification in diabetic mice.
- The therapeutic benefits are achieved without affecting the pituitary-growth hormone axis, suggesting a targeted mechanism.
- MR409 holds promise as a novel pharmacological strategy for managing vascular calcification and associated cardiovascular complications in diabetes.
