Aberrant proliferation of vascular smooth muscle cells (VSMC) is a critical contributor to the pathogenesis of atherosclerosis (AS). Our previous studies have demonstrated that apelin‐13/APJ confers a proliferative response in VSMC, however, its underlying mechanism remains elusive. In this study, we aimed to investigate the role of mitophagy in apelin‐13‐induced VSMC proliferation and atherosclerotic lesions in apolipoprotein E knockout (ApoE‐/‐) mice. Apelin‐13 enhances human aortic VSMC proliferation and proliferative regulator proliferating cell nuclear antigen expression in dose and time‐dependent manner, while is abolished by APJ antagonist F13A. We observe the engulfment of damage mitochondria by autophagosomes (mitophagy) of human aortic VSMC in apelin‐13 stimulation. Mechanistically, apelin‐13 increases p‐AMPKα and promotes mitophagic activity such as the LC3I to LC3II ratio, the increase of Beclin‐1 level and the decrease of p62 level. Importantly, the expressions of PINK1, Parkin, VDAC1, and Tom20 are induced by apelin‐13. Conversely, blockade of APJ by F13A abolishes these stimulatory effects. Human aortic VSMC transfected with AMPKα, PINK1, or Parkin and subjected to apelin‐13 impairs mitophagy and prevents proliferation. Additional, apelin‐13 not only increases the expression of Drp1 but also reduces the expressions of Mfn1, Mfn2, and OPA1. Remarkably, the mitochondrial division inhibitor‐1(Mdivi‐1), the pharmacological inhibition of Drp1, attenuates human aortic VSMC proliferation. Treatment of ApoE‐/‐ mice with apelin‐13 accelerates atherosclerotic lesions, increases p‐AMPKα and mitophagy in aortic wall in vivo. Finally, PINK1‐/‐ mutant mice with apelin‐13 attenuates atherosclerotic lesions along with defective in mitophagy. PINK1/Parkin‐mediated mitophagy promotes apelin‐13‐evoked human aortic VSMC proliferation by activating p‐AMPKα and exacerbates the progression of atherosclerotic lesions.
In the traditional sculpture surface machining process, the G01 code is still the mainstream trajectory. Furthermore, real-time feedrate scheduling and corner smooth algorithm in controller constitute the mainstream method to improve the machining process of short line G01 code in sculpture surface machining. However, the G01 code’s discontinuity and the limits of real-time calculation capacity hinder the use of high-speed machine tools and the accuracy of the machined part. In this article, a new method for sculpture surface machining that considers the advantages and disadvantages of both the computer-aided manufacturing software and the real-time controller is presented to promote the use of a continuous curve tool path. The method mainly transfers the computing-intensive feedrate scheduling and trajectory optimization algorithm in the real-time controller to the computer-aided manufacturing software. Furthermore, the computer-aided manufacturing software generates the machining data, which contain the geometry and feedrate information of the machining process. Finally, the real-time interpolator and the mathematical form of computer-aided manufacturing–generated data are designed simultaneously. In the method, the real-time controller can be designed as simple as possible to release more computing resources to the other real-time intelligent modules. The powerful computational capacity of the software guarantees the optimality of the machining process.
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