FP40-4 PLASMA MATRIX METALLOPROTEINASES ACTIVITY IN HYPERTENSIVE CHILDREN DUE TO 11ß-HSD2 DEFICIENCY ACTIVITY

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP40-Renin-Angiotensin-Aldosterone System/Endocrine Hypertension
Basic/Translational
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:00 AM
Room 135 (Moscone Center)

Poster Board MON-725
Alejandro Martínez-Aguayo*1, Carmen Campino2, Hernan García2, Marlene Aglony2, Carolina Avalos1, Lilian Bolte1, Rodrigo Diaz Bancalari1, Carolina Andrea Loureiro1, Cristian A Carvajal2, Lorena García3, Sergio Lavanderos3 and Carlos E Fardella2
1Pontificia Universidad Católica de Chile, Santiago, Chile, 2Pontificia Universidad Catolica de Chile, Santiago, Chile, 3Universidad de Chile, Santiago, Chile
Background: Hypertension is a major cause of cardiovascular remodeling. In the cardiovascular system, the remodeling of the extracellular matrix is controlled by the matrix metalloproteinases (MMPs). No data exist in hypertensive children due to 11β-HSD2 deficiency activity and remodeling of the extracellular matrix. MMP-9 has significant effects on important biologically active proteins and peptides, such as TGF-β and other “profibrotic” proteins and their pathways. MMP-2 degrades basement membrane proteins, fibrillar collagen peptides, and newly synthesized collagen fibers.

Objective:To elucidate the behavior of plasma MMP-9 and MMP-2 activities in hypertensive children with 11β-HSD2 deficiency activity compared with hypertensive children with normal enzyme activity matched by BMI percentile

Design: Cross- sectional study.

Subjects and methods: Hypertensive (n=102) children (5-16 years old) were studied. Systolic and diastolic blood pressure indexes (SBPi & DBPi) were calculated using the observed blood pressure/percentile 50th(for gender, height and age). Fasting serum cortisol (F) and cortisone (E) concentration were measured by RIA and the 11β-HSD2 activity was estimated by F/E ratio. 11β-HSD2 deficiency activity was considered when F/E ratio ≥4.3 (mean +2 SD in 93 normotensive subjects (1)). Plasma MMP-9 and MMP-2 activities were evaluated by zymography. Their results were expressed as number of changes respect to the reference plasma used as internal control. Of these hypertensive children 18/102 (17.6%) had F/E ratio≥4.3 (Group A, n=18). They were selected and were compared with a group of hypertensive children with F/E ratio<4.3 (Group B, n=18) matched by BMI percentile. The results were expressed as median [Q1-Q3] and compared by Mann Whitney test.

Results: Group A and Group B showed similar age, 10.9 [7.7 – 12.9] vs 12.2 [10.3-14.1] years; P= 0.184). Group A had higher SBP index than Group B (1.24 [1.18–1.29] vs 1.14 [1.11- 1.18]; P <0.001); but they had similar DBP index (1.25 [1.12–1.37] vs 1.17 [1.06-1.23]; P=0.078). Plasma MMP-9 and MMP-2 activities were higher in Group A than Group B (2.87 [2.02–3.09] vs 1.97 [1.37-2.34]; P=0.0124and 1.97[1.7–2.34] vs 1.55 [1.02-1.70]; p=0.018, respectively

Conclusion: As far as we know, this is the first report showing an increase MMP-9 and MMP-2 activities in hypertensive children with high F/E ratio, suggesting that these patients have early and higher remodeling of the extracellular matrix.

(1) C. Campino, A. Martinez-Aguayo, R. Baudrand, C. A.Carvajal, M. Aglony, H. Garcia, O. Padilla, A.M. Kalergis, C.E. Fardella. Age-related changes in 11β-hydroxysteroid dehydrogenase type 2 activity in normotensive subjects. American Journal of Hypertension in press.

Nothing to Disclose: AM, CC, HG, MA, CA, LB, RDB, CAL, CAC, LG, SL, CEF

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This work was supported by the following Chilean grants: Fondecyt 1100356 and 1130427, Fondef D08I1087; Fondef Idea CA12i10150  and Millenium P09/016-F