Doxycycline prevents intimal hyperplasia in vitro and may improve patency of the internal thoracic artery.
OBJECTIVE
The development of intimal hyperplasia and graft failure is an important problem in cardiac surgery. A fundamental process in intimal hyperplasia is the degradation of extracellular matrix by metalloproteases which induces the vascular smooth-muscle cells migration and sets the scene for graft atherosclerosis. This study investigated whether doxycycline, a metalloproteases inhibitor, can prevent the intimal hyperplasia occurrence in cultured human internal mammary artery, thus extending graft patency.


METHODS
Segments of internal mammary artery from 20 consecutive patients were prepared and cultured for 2 weeks in serum-supplemented medium (control) or in medium supplemented with 10⁻⁵  M and 10⁻⁶ M doxycycline concentrations. Tissues were fixed, sectioned, and stained, and neointimal thickness was measured by computer-aided image analysis. Further sections were cultured and prepared for gel enzymography to measure the matrix metalloproteinase-2 and -9 levels.


RESULTS
At the end of the culture period, neointimal thickness was significantly (P = 0.001) dose-dependently reduced in samples treated with doxycycline when compared with controls. Gelatin enzymography demonstrated a reduction in values for both latent and active forms of metalloproteases.


CONCLUSIONS
Doxycycline, in a model of internal mammary artery intimal hyperplasia, has a specific role in inhibiting metalloproteases activity and may prevent graft stenosis.
Department of Cardiac Surgery, School of Medicine, University Federico II, Via S. Pansini 5, 80131 Naples, Italy.
Vito
V
Mannacio
Luigi
L
Di Tommaso
Anita
A
Antignano
Ettorino
E
Di Tommaso
Paolo
P
Stassano
Carlo
C
Vosa
D045744:Cell Line, Tumor; D004318:Doxycycline / Q000494:pharmacology* / Q000627:therapeutic use*; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D008323:Mammary Arteries / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D014654:Vascular Patency / Q000187:drug effects
D005780:Gelatin; D004318:Doxycycline