Chinese medicine and intermittent fasting integration therapy attenuate diabetic vascular calcification via miR21-5p/Tpm1-mediated osteogenic differentiation of VSMCs

Available online 13 November 2025

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Vascular calcification (VC) is a marker of substantial vascular damage in patients with diabetes and has been recognized as a predictor of cardiovascular events and all-cause mortality. To date, no effective therapeutic strategy has been formulated for the management of VC. In this study, we integrated the treatment regimen of the Danlian-Tongmai (DLTM) formula, a traditional Chinese medicine (TCM) with anti-diabetic VC (anti-DVC) effects with intermittent fasting (IF), and established the Chinese medicine and intermittent fasting integration therapy (CMIT). CMIT synergistically enhanced the regulation of calcium-phosphorus homeostasis and vascular repair, and demonstrated significantly greater efficacy than DLTM or IF monotherapy in inhibiting calcium deposition and osteogenic differentiation both in vivo and in vitro. Transcriptomic sequencing revealed that the miR21-5p/Tpm1 axis mediated the anti-calcification effect of CMIT. MiR21-5p promoted the overproliferation, migration, and osteogenic differentiation of vascular smooth muscle cells (VSMC) by negatively regulating Tpm1, while CMIT inhibited such processes. In conclusion, this study demonstrated that CMIT inhibited the osteogenic differentiation of VSMC and restored its contractile phenotype by inhibiting the activation of the miR21-5p/Tpm1 axis, thus exerting a therapeutic effect on DVC. CMIT may be a promising approach for the treatment of DVC.

Graphical abstractChinese medicine and intermittent fasting integration therapy effectively inhibits VSMC osteogenic differentiation by regulating the miR21-5p/Tpm1 axis, thereby achieving a synergistic anti-diabetic vascular calcification effect.