Shear stress modulates VCAM-1 expression in response to TNF-α and dietary lipids via interferon regulatory factor-1 in cultured endothelium.

Dyslipidemia is a primary risk factor for cardiovascular disease, but the specific mechanisms that determine the localization of atherosclerotic plaques in arteries are not well defined. Triglyceride-rich lipoproteins (TGRL) isolated from human plasma after a high-fat meal modulate TNF-α-induced VCAM-1 expression in cultured human aortic endothelial cells (HAECs) via an interferon regulatory factor (IRF)-1-dependent transcriptional mechanism. We examined whether fluid shear stress acts as a mediator of IRF-1-dependent VCAM-1 expression in response to cytokine and dietary lipids. IRF-1 and VCAM-1 were examined by immunofluorescence in TNF-α-stimulated HAEC monolayers exposed to TGRL and a linear gradient of shear stress ranging from 0 to 16 dyn/cm(2) in a microfluidic device. Shear stress alone modulated TNF-α-induced VCAM-1 expression, eliciting a 150% increase at low shear stress (2 dyn/cm(2)) and a 70% decrease at high shear stress (12 dyn/cm(2)) relative to static. These differences correlated with a 60% increase in IRF-1 expression under low shear stress and a 40% decrease under high shear stress. The addition of TGRL along with cytokine activated a fourfold increase in VCAM-1 expression and a twofold increase in IRF-1 expression. The combined effect of shear stress and TGRL on the upregulation of membrane VCAM-1 was abolished by transfection of HAECs with IRF-1-specific small interfering RNA. In a healthy swine model, elevated levels of endothelial IRF-1 were also observed within atherosusceptible regions of the aorta by Western blot analysis and immunohistochemistry, implicating arterial hemodynamics in the regulation of IRF-1 expression. These data demonstrate direct roles for fluid shear stress and postprandial TGRL from human serum in the regulation of IRF-1 expression and downstream inflammatory responses in HAECs.

Clinical and Biochemical Correlation of Intra-articular Platelet-Rich Plasma and Corticosteroid Using Serum Matrix Metalloproteinase 3 (MMP-3) Levels in Osteoarthritis of Knee.

Introduction Osteoarthritis (OA) in humans is an inevitable consequence of ageing and can now be effectively managed with advancements in knowledge and understanding of the disease. The major concern in a patient suffering from this disease is the functional impairment caused by the pain. The goals in the management of OA knee include symptom relief with preservation of joint function. Despite there being a number of studies on the effectiveness of PRP and CS for knee OA, most of them have focused on patient-reported functional outcomes only. Hence, we conducted this study to assess the potential and effectiveness of a single intra-articular injection of PRP and CS in the functional improvement of knee OA patients using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Visual Analogue Scale (VAS) and to establish the bio-modulatory effects of intra-articular PRP and CS in knee OA patients by estimating the serum matrix metalloproteinase-3 (MMP-3) levels. Methodology Patients attending the outpatient department with complaints of knee pain were screened. Standing anteroposterior and lateral radiographs of the knees were obtained. Patients with Kellgren and Lawrence (K-L) grades II and III were enrolled in our study. A total of 96 patients were included in the study after fulfilling the inclusion and exclusion criteria. Patients were divided into two groups (PRP and CS) by randomisation. There were 48 each in the PRP and CS groups, out of which nine were lost to follow-up, two from the PRP group and seven from the CS group. A total of 87 patients fulfilling the inclusion criteria were finally enrolled in the study and followed up for nine months after a single intra-articular injection. The biochemical assessment of serum levels of MMP-3 was done at baseline and in the ninth month. Accordingly, patients in the PRP group were injected with freshly prepared PRP (3 ml) within two hours of preparation, whereas those in the CS received 80 mg of methylprednisolone acetate. VAS and WOMAC were measured at baseline, and then in the first, third, sixth, and ninth month post-injection follow-ups. MMP-3 level was estimated before the injection and at the ninth-month post-injection follow-up. Data collected for both groups were analysed and compared with each other. Conclusion PRP is unquestionably a better option than CS in OA of the knee based on boosting functional activity, lowering stiffness, and reducing pain, all three of which are denoted by the WOMAC and VAS scores as the effect of PRP lasts longer than CS injections for the aforesaid issues. We could not find any significant change in levels of MMP3 post PRP and CS injections, which signifies that these two modalities do not have any effect in either preventing cartilage degeneration or promoting cartilage regeneration. Our findings have shown that PRP injections are safe, minimally invasive, and effective treatment modalities for OA knee.