Regulatory Extracellular Matrix Research Articles

Periostin's role in uterine leiomyoma development: a mini-review on the potential periostin poses as a pharmacological intervention for uterine leiomyoma.

Uterine leiomyomas, also known as fibroids or myomas, occur in an estimated 70-80% of reproductive aged women. Many experience debilitating symptoms including pelvic pain, abnormal uterine bleeding (AUB), dyspareunia, dysmenorrhea, and infertility. Current treatment options are limited in preserving fertility, with many opting for sterilizing hysterectomy as a form of treatment. Currently, surgical interventions include hysterectomy, myomectomy, and uterine artery embolization in addition to endometrial ablation to control AUB. Non-surgical hormonal interventions, including GnRH agonists, are connotated with negative side effects and are unacceptable for women desiring fertility. Periostin, a regulatory extra cellular matrix (ECM) protein, has been found to be expressed in various gynecological diseases including leiomyomas. We previously determined that periostin over-expression in immortalized myometrial cells led to the development of a leiomyoma-like cellular phenotype. Periostin is induced by TGF-β, signals through the PI3K/AKT pathway, induces collagen production, and mediates wound repair and fibrosis, all of which are implicated in leiomyoma pathology. Periostin has been linked to other gynecological diseases including ovarian cancer and endometriosis and is being investigated as pharmacological target for treating ovarian cancer, post-surgical scarring, and numerous other fibrotic conditions. In this review, we provide discussion linking pathological inflammation and wound repair, with a TGF-β-periostin-collagen signaling in the pathogenesis of leiomyomas, and ultimately the potential of periostin as a druggable target to treat leiomyomas.

Abstract 19387: Extracellular Matrix Remodelling in Porcine Coronary Arteries Upon Stent Implantation

Introduction: Extracellular matrix (ECM) remodeling upon vascular stent injury contributes to both neointimal hyperplasia (restenosis) as well as endothelialization (propensity for thrombosis). Despite its important clinical implications little is known about ECM changes post stent implantation. Hypothesis: ECM remodelling, a determinant of stent healing, differs between drug-eluting (DES) and bare-metal stents (BMS). Methods: Using proteomics, we profile changes of vascular ECM proteins over time following implantation of DES and BMS in porcine coronary arteries in an overstretch model. Results: DES (n=14) or BMS (n=14) were implanted in coronary arteries of pigs. Quantitative coronary angiography and optical coherence tomography were performed at 1, 3, 7, 14 and 28 days after stent deployment. Animals were sacrificed at each of these time-points and their coronary arteries were retrieved for subsequent analysis by proteomics. A total of 126 ECM and ECM-associated proteins were identified by mass spectrometry. Within the first week after stent injury, proteins involved in inflammation and thrombosis were elevated in DES and BMS stented arteries. After one week, significant changes in regulatory ECM proteins such as small leucine rich proteins or matricellular proteins were observed. By day 28, differences between BMS and DES became apparent: basement membrane proteins as markers of cellularity were reduced in DES compared with BMS. In contrast, large aggregating proteoglycans such as aggrecan and versican were increased. Both belong to the lectican protein family that act as linkers of ECM molecules with their highly charged glycan side chains. The proteomics findings were validated by immunoblot analysis and real-time polymerase chain reaction. We were also able to detect aggrecan by immunohistochemistry in clinical specimen confirming differential expression patterns of aggrecan and versican in stented human coronary arteries. Conclusions: In the early course after BMS and DES implantation the ECM changes were similar. Significant differences were identified in the regulation of ECM proteins in long-term follow-up consisting of suppression of basement membrane proteins and up-regulation of large aggregating proteoglycans in DES.