The mechanical force caused by elevated blood pressure plays a decisive role in vascular differentiation and development, the maintenance of normal vascular structure and function, and the process of vascular lesions. Abnormal elevation of blood lipid and/or blood glucose synergistically accelerate mechanical force-initiated vascular remodeling and the occurrence and development of diseases. Mechanical forces can nonspecifically activate all transmembrane protein molecules in vascular cells, leading to simultaneous activation of intracellular multi-signal channel molecules (secondary effector molecules). The upstream multi-pathway molecular signals converge on the node molecules of signal network and then diverge to the downstream pathway molecules, and finally start more signaling pathway activation, and amplify the signal cascades. Then, a series of pathophysiological changes such as cell differentiation, migration, inflammation, phenotypic changes, calcification, proliferation, and apoptosis occur. Finally, the structural and functional changes of blood vessels, such as atherosclerosis, become the main cause of death and disability caused by cardiovascular and cerebrovascular diseases. This paper reviews the research progress from this research group and international peers, that is, vascular remodeling is closely related to the effect of mechanical force generated by elevated blood pressure on vascular smooth muscle cells.