Clinical Significance of Neonatal Lenticulostriate Vasculopathy: Association with Congenital Cytomegalovirus Infection

PURPOSE: To investigate clinical characteristics of neonates with lenticulostriate vasculopathy (LSV) and determine the correlation between LSV and clinical characteristics, especially congenital cytomegalovirus (CMV) infection. METHODS: We retrospectively reviewed the medical records of neonates with LSV, born at Cheil General Hospital between January 2005 and December 2015. LSV was graded into three groups based on the number of the LSV lesions and classified into an isolated and combined group showing LSV with coexistent abnormalities noted on brain sonography. We compared clinical data based on the LSV classification. RESULTS: Our study included 102 neonates with LSV, which showed an unilateral pattern in 10 and bilateral pattern in 92 neonates. The numbers of neonates studied based on LSV grading were 33, 53, and 16 in grade 1, 2, and 3, respectively. We observed the isolated LSV in 62 and the combined type in 40 neonates. We observed that 93 (91.2%) of the neonates with LSV did not show specific underlying cause for this condition. Congenital CMV infection was detected in 7 neonates, including 0, 5, and 2 neonates belonging to grade 1, 2, and 3, respectively. Among these, 2 neonates showed the isolated, and 5 showed the combined type of LSV. Statistically, congenital CMV infection was more significantly associated with LSV in grade 2 and 3 than in grade 1 (P < 0.05). Additionally, congenital CMV infection was more commonly observed in the combined than in the isolated LSV type showing a marginal association (P=0.07). CONCLUSION: We observed that LSV was not clinically significant except when associated with CMV infection. We suggest that neonates presenting with a grade 2 or higher of LSV or a combined type of LSV detected via neonatal brain ultrasonography should be evaluated for CMV infection.

Impact of Lysophosphatidylcholine on the Plasminogen Activator System in Cultured Vascular Smooth Muscle Cells

The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-kappaB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-kappaB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-kappaB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.