Abstract
Elevated plasma homocysteine (Hcy) levels have been associated with several tissue injuries including heart and liver fibrosis. In these diseases, hyperhomocysteinemia (Hhcy) plays a major role in modulating the alteration of the balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs), leading to the pathological accumulation of extracellular matrix (ECM) proteins. Since the effect of Hhcy on ECM of seminal vesicle was not studied, the aim of our research was to check if Hcy can induce a remodeling within seminal vesicles ECM. The study was conducted in 22 adult male Wistar rats. The rats were divided into two groups: a control group, which received standard diet and tap water; the treated group received the same diet and water supplemented with solution of L-methionine (200 mg/kg b.w./day) for 6 months. Plasma homocysteine concentration was measured. Histological changes were observed with light microscope. The presence of collagen I and III and metalloproteinases (2, 3, 7 and 9) in the seminal vesicles was examined using immunohistochemistry and Western blotting. Plasma Hcy levels increased significantly after methionine treatment and interfered significantly with body weight in treated rats. The content of fibrillar collagens (I and III) in the wall of seminal vesicles was elevated in hyperhomocysteinemic rats. Moreover, we found that hyperhomocysteinemia increased the expression of MMP-2, -3, -7 and -9 in seminal vesicles of experimental rats. Increased plasma concentration of Hcy accompanied by the accumulation of collagen and upregulation of MMPs in rat seminal vesicles might contribute to the remodeling of seminal vesicles.
Highlights
Elevated plasma homocysteine (Hcy) levels have been associated with several tissue injuries including heart and liver fibrosis
Increased plasma concentration of Hcy accompanied by the accumulation of collagen and upregulation of Matrix metalloproteinases (MMPs) in rat seminal vesicles might contribute to the remodeling of seminal vesicles
Homocysteine (Hcy) is a sulfur containing amino acid formed during the metabolism of methionine, an essential amino acid derived from the diet [1]
Summary
Elevated plasma homocysteine (Hcy) levels have been associated with several tissue injuries including heart and liver fibrosis. In these diseases, hyperhomocysteinemia (Hhcy) plays a major role in modulating the alteration of the balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs), leading to the pathological accumulation of extracellular matrix (ECM) proteins. Increased plasma concentration of Hcy accompanied by the accumulation of collagen and upregulation of MMPs in rat seminal vesicles might contribute to the remodeling of seminal vesicles. Previous studies have revealed that these processes induced by Hhcy were associated with initiation and progression of fibrosis characterized by an accumulation of extracellular matrix (ECM) proteins, collagen and an imbalance of MMPs/TIMPs system, which plays a determinant role in the regulation of collagen tissue turnover [7, 8]. MMPs are implicated in remodeling of many connective tissues in physiological and pathological processes such as reproduction, embryonic development, morphogenesis, angiogenesis and fibrosis of such organs as liver, kidney and pulmonary [13,14,15,16,17,18]
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