SUMO Wrestling Runx2 as a Strategy to Inhibit Arteriosclerotic Calcification
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- diabetes mellitus, type II
- renal insufficiency, chronic
- vascular calcification
With our increasingly aged and dysmetabolic population, the deleterious consequences of globally perturbed calcium metabolism become increasingly apparent.1 Net loss of bone mineral quantity and quality increases risk for osteoporotic fracture,2 whereas accumulating arterial calcium loads stiffen conduit arteries and impairs Windkessel physiology—the rubbery elasticity of conduit vessels that ensures smooth distal tissue perfusion throughout the cardiac cycle.3 Murine models were first used to identify that reciprocal change in skeletal versus vascular calcium accrual can occur in response to the dysmetabolic states of diabetes mellitus, uremia, and dyslipidemia4. However, the Multiethnic Study of Atherosclerosis (MESA) firmly established the general connection between accrual of metabolic syndrome parameters—impaired fasting glucose, hypertension, obesity, low high-density lipoprotein, hypertriglyceridemia, or frank type 2 diabetes mellitus (T2D)—and arterial calcium load in humans.5 Recent studies implementing high-resolution peripheral quantitative computed tomography have shown that older men and women with T2D exhibit greater cortical bone porosity—a feature that compromises bone strength and increases fracture risk.6,7 Patients with calcified peripheral arterial disease also exhibit deficiencies in trabecular bone structure on high-resolution peripheral quantitative computed tomography, further solidifying the relationship.8 Elegant human genetic studies by Mani et al9 highlighted that osteoporosis–atherosclerosis relationships are genetically determined in part by LRP6 signaling—with the cell-autonomous (osteoblast and vascular smooth muscle) contributions of …