The involvement of inflammatory mechanisms in the progression of atherosclerosis has recently been suggested. Monocyte chemotactic protein 1 (MCP-1) is a soluble protein which is implicated in acute and chronic inflammatory processes, including atherosclerosis. We evaluated the effect of human recombinant MCP-1 on the in vitro proliferation of rat vascular smooth muscle cells (VSMCs). Incubation of VSMCs with MCP-1 (50-200 ng/ml) in the presence of 0.5% FCS significantly increased cell proliferation, [3H]-thymidine incorporation and the proliferative S fraction, measured by flow cytometry, compared to control cells. The proliferative effect of MCP-1 was specific, as shown by inhibition with a rabbit polyclonal serum to MCP-1. Moreover, the mitogenic effect of MCP-1 was significantly inhibited by downregulation of protein kinase C (PKC) activity and by incubation with H-7, a protein kinase inhibitor, suggesting the involvement of the PKC system. Verapamil, a Ca2+ channel blocker, also reduced the stimulatory effect of MCP-1 on cell proliferation. This study demonstrates that MCP-1 does not merely have a chemotactic activity, but also a mitogenic effect on cultured rat VSMCs.

Animals↗

PubMedDate not supplied

Simple renal cysts in hypertensive patients: relation between cyst growing and anti-hypertensive therapy.

The study investigates relationship between simple renal cyst enlargement studied by ultrasonography and anti-hypertensive treatment. To this purpose we enrolled 42 patients with newly diagnosed hypertension affected by simple renal cysts. Fourteen were randomly assigned to treatment with ACE-Inhibitors (group 1), twelve to diuretics (group 2) and sixteen to Ca-Antagonists (group 3). Patient performed a basal ultrasonography to evaluate basal cyst dimension before starting anti-hypertensive treatment. Following 12 months of the anti-hypertensive regimen, a new echograph was performed to evaluate changes in cyst size. A control group consisting of 15 patients with normal blood pressure and simple renal cysts was enrolled (group 0). An enlargement of cysts was detected in all patients. However, the enlargement observed in patients treated by Ca-Antagonists was significantly greater than that observed in the other groups (p<0.05). Our study supports the hypothesis that Ca-Antagonists may favor cyst enlargement by enhancing cyclic AMP production. In fact, cAMP and cAMP agonists stimulate fluid secretion by lining cells of the cyst wall, inducing cyst enlargement.

Aged↗

PubMedDate not supplied

Relationship between reduced BCL-2 expression in circulating mononuclear cells and early nephropathy in type 1 diabetes.

Microalbuminuria is the earliest clinical evidence of diabetic nephropathy, but the mechanisms linking hyperglycemia and kidney complications are not clear. The aim of this study was to evaluate whether enhanced oxidative stress in patients with microalbuminuria can contribute to diabetic nephropathy development through downregulation of the antiapoptotic gene Bcl-2 that promotes in turn a pro-inflammatory status. We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared to 15 matched healthy controls. Plasma oxidant status, and expression of Bcl-2, activated NF-kB, inducible Nitric Oxide synthase (iNOS), and monocyte chemoattractant protein (MCP)-1 in circulating monocytes were evaluated at baseline and after 8-week oral vitamin E treatment (600 mg b.i.d.). Bcl-2 expression was significantly reduced in microalbuminuric diabetic patients as a consequence of increased oxidant burden secondary to persistent hyperglycemia. Bcl-2 down-regulation was associated with enhanced expression of NF-kB, iNOS and MCP-1, and showed a strong correlation with the albumin excretion rate. Low Bcl-2 expression and high inflammatory status were normalized by vitamin E both in vivo and in vitro. Our study showed that Bcl-2 down-regulation in diabetic patients with poor glycemic control results in the activation of the NF-kB pathway leading to the development of nephropathy. Vitamin E might provide a novel form of therapy for prevention of nephropathy in diabetic patients in which an acceptable glycemic control is difficult to achieve despite insulin therapy.

Adolescent↗