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

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 <i>in vivo</i> and <i>in vitro</i>. Transcriptomic sequencing revealed that the <i>miR21-5p</i>/<i>Tpm1</i> axis mediated the anti-calcification effect of CMIT. <i>MiR21-5p</i> promoted the overproliferation, migration, and osteogenic differentiation of vascular smooth muscle cells (VSMC) by negatively regulating <i>Tpm1</i>, 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 <i>miR21-5p</i>/<i>Tpm1</i> axis, thus exerting a therapeutic effect on DVC. CMIT may be a promising approach for the treatment of DVC.