Abstract 1035: Functional Polymorphism of the Matrix Metalloproteinase 1 Gene Promoter (-1607 1G/2G) Predicts Carotid Intra-plaque Hemorrhage in Patients Submitted to Endarterectomy
Introduction: Carotid intraplaque hemorrhage is a marker of atheroma instability. Matrix metalloproteinase (MMP)-1 and -3 are proteolytic enzymes that degrade extracellular matrix components, leading to structural instability of vulnerable plaques.
Hypothesis: We hypothesize that funcional polymorphisms of the MMP-1 and MMP-3 genes could identify patients prone to atheroma bleeding in the carotid artery.
Methods: Consecutive patients submitted to carotid endarterectomy underwent high-resolution magnetic resonance imaging (MRI) - to evaluate the presence of a hyperintense signal on the T1-weighted sequence - and histological analysis - to assess the presence of intraplaque bleeding (stained by hematoxylineosin and Mallory trichromic). Genotyping of MMP-1 polymorphisms at nucleotide -1607 (1G/2G) and of MMP-3 at nucleotide -1612 (5A/6A) was performed by polymerase chain reaction with restriction fragment length polymorphism analysis.
Results: We evaluated 48 predominantly male (63%) and hypertensive (88%) patients (66 ± 9 years-old). Intraplaque hemorrhage was identified in 30 (62.5%) patients by histology and classified as acute in 17 (35.4%), recent in 11 (22.9%) and late in 2 (4.2%) patients. There was an excellent agreement between acute or recent hemorrhage on histology and the presence of a hyperintense signal at MRI (kappa coefficient of 0.91, 95% confidence interval of 0.75–1.00). MMP-1 genotypes were 1G/1G in 7 (15%) subjects, 1G/2G in 30 (62%) and 2G/2G in 11 (23%) patients. MMP-3 genotypes were 5A/5A in 6 (12%) subjects, 5A/6A in 30 (63%) and 6A/6A in 12 (25%) patients. No significant association between MRI findings and MMPs genotypes was observed. However, carriers of the 2G allele, responsible for a greater proteolyic activity of MMP-1, were more prevalent in plaques with signs of hemorrhage on hystology compared to patients without intraplaque bleeding (28 out 30 [93%] versus 13 out of 18 [72%], respectively, p = 0.045). No interaction was observed between MMP-3 genotypes and carotid intraplaque hemorrhage (all p values > 0.2).
Conclusions - In conclusion, our data indicate that genetically mediated variability in MMP-1 activity may be involved in the events that lead to intraplaque hemorrhage.