A1146 Aldosterone facilitates high phosphate-induced vascular calcification via upregulation of osteogenic factors

Objectives: Vascular calcification (VC) is closely associated with cardiovascular mortality. Recent experiments suggest an association between aldosterone and VC. However, the role of aldosterone in human VC remains unclear. Osteogenic phenotypic switch of vascular smooth muscle cells (VSMCs) is a widely accepted mechanism of VC. This study aimed to confirm the association between aldosterone and VC in human studies and to explore whether Methods: Data of 1325 participants from the Framingham Heart Study (FHS) and 80 patients with confirmed primary aldosteronism (PA) from our center were assessed. Both coronary artery calcification (CAC) and abdominal aortic calcification (AAC) were measured by computed tomographic scanning. Antibody-based protein array was used to detect bone metabolism factors. Primary rat VSMCs were treated with Results: Surprisingly, both FSH data and our study showed no association between CAC/AAC and plasma aldosterone concentration (PAC). However, participants with higher PAC tended to develop AAC when the estimated glomerular filtration rate (eGFR) lower than 90 mL/min × 1.73m2 (P < 0.01). Serum levels of bone osteogenic factors, including bone morphogenetic proteins and osteopontin, were significantly higher only in PA patients with impaired eGFR (all P < 0.01). In vitro studies demonstrated that aldosterone only induced calcification in the presence of high phosphate conditions. Moreover, aldosterone significantly decreased expression of contractile markers, and increased expression of osteogenic markers of VSMCs (all P < 0.01). Conclusion: AAC was closely associated with upregulation of osteogenic factors in PA patients with impaired eGFR. Aldosterone excess promoted high phosphate-induced VSMC osteogenic differentiation and subsequent calcification. We define a putative mechanism linking ald