Tortuous arteries and veins are commonly observed in humans and animals. While mild tortuosity is asymptomatic, severe tortuosity can lead to ischemic attack in distal organs. Clinical observations have linked tortuous arteries and veins with aging, atherosclerosis, hypertension, genetic defects and diabetes mellitus. However, the mechanisms of their formation and development are poorly understood. This review summarizes the current clinical and biomechanical studies on the initiation, development and treatment of tortuous blood vessels. We submit a new hypothesis that mechanical instability and remodeling could be mechanisms for the initiation and development of these tortuous vessels.

Rationale:: Matrix metalloproteinase (MMP)-28 regulates the inflammatory and extracellular matrix responses in cardiac aging, but the roles of MMP-28 after myocardial infarction (MI) have not been explored. Objective:: To determine the impact of MMP-28 deletion on post-MI remodeling of the left ventricle (LV). Methods and Results:: Adult C57BL/6J wild-type (n=76) and MMP null (MMP-28 ^−/− , n=86) mice of both sexes were subjected to permanent coronary artery ligation to create MI. MMP-28 expression decreased post-MI, and its cell source shifted from myocytes to macrophages. MMP-28 deletion increased day 7 mortality because of increased cardiac rupture post-MI. MMP-28 ^−/− mice exhibited larger LV volumes, worse LV dysfunction, a worse LV remodeling index, and increased lung edema. Plasma MMP-9 levels were unchanged in the MMP-28 ^−/− mice but increased in wild-type mice at day 7 post-MI. The mRNA levels of inflammatory and extracellular matrix proteins were attenuated in the infarct regions of MMP-28 ^−/− mice, indicating reduced inflammatory and extracellular matrix responses. M2 macrophage activation was impaired when MMP-28 was absent. MMP-28 deletion also led to decreased collagen deposition and fewer myofibroblasts. Collagen cross-linking was impaired as a result of decreased expression and activation of lysyl oxidase in the infarcts of MMP-28 ^−/− mice. The LV tensile strength at day 3 post-MI, however, was similar between the 2 genotypes. Conclusions:: MMP-28 deletion aggravated MI-induced LV dysfunction and rupture as a result of defective inflammatory response and scar formation by suppressing M2 macrophage activation.