Is the Expression of the Components of the Carotid Matrix of Rats Influenced by Estrogen, Progestin and Tibolone?

Abstract

Objective To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries. Methods A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by real-time polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries. Results The groups showed significant differences on mRNA HPSE expression (p = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups. Conclusion Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.

Proteoglycans in the Pathogenesis of Hormone-Dependent Cancers: Mediators and Effectors

“…Thus, the different ECM proteins form and remodel complex nets, producing compartments which topically regulate the bioavailability of active mediators that affect cancer cell growth, survival, migration, and invasion. Indeed, PGs, with their versatile structure, contribute significantly to the generation of hormone/growth factor concentration gradients in the ECM and, by extension, in the TME [ 193 , 194 ].…”

Spontaneous coronary artery dissection in the context of tamoxifen; Is there any correlation?

“…This includes changes in the balance of elastic fiber and mucopolysaccharide content, smooth muscle hypertrophy/hyperplasia, and mucinous cystic necrosis, all of which contribute to the development of SCAD. 16,[20][21][22][23][24][25] Clinical presentations of SCAD often mimic atherosclerotic ACS. The typical SCAD patient is a middle-aged woman with no classic cardiovascular risk factors, with women accounting for 87%-95% of SCAD cases, and the average age at diagnosis is between 44 and 53 years old.…”

“…However, it appears that tamoxifen, through its effects on estrogen receptors (ERα, ERβ, GPER), heparanase (HPSE), extracellular matrix proteases (MMPs), angiotensin‐II receptor type 1 (AT1R), and endothelin‐1 receptor type A (ETAR) at the cellular level, induces secondary alterations in the structure and integrity of the vascular endothelium. This includes changes in the balance of elastic fiber and mucopolysaccharide content, smooth muscle hypertrophy/hyperplasia, and mucinous cystic necrosis, all of which contribute to the development of SCAD 16,20–25 …”