Role of Klotho in migration and proliferation of human dermal microvascular endothelial cells.

PURPOSE: To examine the possible role of Klotho (Kl) in human microvasculature. METHODS: The expression level of Kl in primary human dermal microvascular endothelial cells (HDMECs) and primary human dermal fibroblasts (HFb) was detected by real-time polymerase chain reaction amplification (qRT-PCR), Western blot analyses and immunohistochemistry. Migration of HDMECs and HFb was examined in monolayer wound healing "scratch assay" and Transwell assay. Proliferation of these cells was examined using Cell Proliferation BrdU incorporation assay. RESULTS: Our results have shown that downregulation of Kl abrogated HDMECs migration after 48h. On the other hand, migration of HFb significantly increased after blocking Kl. Lack of Kl decreased expression of genes involved in the activation of endothelial cells and enhanced expression of genes involved in extracellular matrix remodeling and organization of connective tissue. CONCLUSIONS: This study for the first time provides the evidence that Kl is expressed in HDMECs and HFb. Additionally, we have demonstrated that Kl is implicated in the process of angiogenesis of human dermal microvasculature.

Are microparticles the missing link between thrombosis and autoimmune diseases? Involvement in selected rheumatologic diseases.

Microparticles (MPs) are membrane-bound vesicles with important physiologic effects. MPs exchange information intercellularly, with each kind of MP carrying antigens and receptors of the cells from which they originated. They are biologic effectors in inflammation, angiogenesis, vascular injury, and thrombosis. Thrombosis is generally caused by abnormalities in blood flow, blood composition, and/or properties of the vessel wall. Thrombosis is a well-described feature of cardiovascular disease and cerebrovascular disease. Accumulating evidence suggests that increased risk of thrombosis is also characteristic of autoimmune disorders and immune-mediated diseases affecting all age groups, although the older adults are most vulnerable. Current research has also implicated MPs as a source of autoantigenic nuclear material that can form immune complexes, activate the innate immune system, and may lead to autoimmunity. This review focuses on the contribution of MPs to both the pathogenesis of autoimmune diseases and, as the immune and coagulation systems are tightly linked, their role in hypercoagulability in the setting of autoimmunity in an aging population.

Impact of endothelial microparticles on coagulation, inflammation, and angiogenesis in age-related vascular diseases.

Endothelial microparticles (EMPs) are complex vesicular structures that originate from plasma membranes of activated or apoptotic endothelial cells. EMPs play a significant role in vascular function by altering the processes of inflammation, coagulation, and angiogenesis, and they are key players in the pathogenesis of several vascular diseases. Circulating EMPs are increased in many age-related vascular diseases such as coronary artery disease, peripheral vascular disease, cerebral ischemia, and congestive heart failure. Their elevation in plasma has been considered as both a biomarker and bioactive effector of vascular damage and a target for vascular diseases. This review focuses on the pleiotropic roles of EMPs and the mechanisms that trigger their formation, particularly the involvement of decreased estrogen levels, thrombin, and PAI-1 as major factors that induce EMPs in age-related vascular diseases.

Prospective randomized study comparing the clinical outcomes between inferior vena cava Greenfield and TrapEase filters.

OBJECTIVE: Although anticoagulation remains the mainstay of treatment for deep venous thrombosis, the use of inferior vena cava (IVC) filters when anticoagulation has failed or when contraindicated remains a safe and effective treatment. Greenfield (Boston Scientific, Natick, Mass) and TrapEase (Cordis, Bridgewater, NJ) filters are arguably among the most popular filtration devices. The Greenfield filter (12F introducer) has been in use for >30 years and has been well studied. The TrapEase filter (6F introducer) has been used since 2000, with a limited number of studies. Good guidelines to help determine which filter to use in any given situation are lacking; therefore, this randomized study prospectively compared the clinical outcomes (access-site thrombosis, filter thrombosis, and symptomatic pulmonary embolism [PE]) between these filters. METHODS: Between July 2006 and November 2008, 156 patients (63 men, 93 women; mean age, 75 years; range, 38-101 years) were randomized: 84 to Greenfield and 72 to TrapEase IVC filter insertion in the infrarenal position using angiographic guidance. Postoperative follow-up comprised serial lower extremity and IVC/iliac vein (IV) duplex imaging (78.2%) at day 1, week 1, every 3 months for the first year, and every 6 months for the second year; clinical evaluation, and clinic visits. During this period, 349 patients (143 men, 206 women; mean age, 75 years; range, 24-96 years) were not randomized. RESULT: The indications for filter placement, in the 156 randomized patients, were gastrointestinal bleeding, 37; intracranial hemorrhage, 12; free-floating clot, 19; failure of anticoagulation, 29; PE, 27; prophylactic, 4; and others, 32. During a mean 12-month follow-up (range, 0-39 months), symptomatic IVC/IV thrombosis developed in five patients (6.94%) in the TrapEase group and none in the Greenfield group (P = .019). No filter migration, access-site thrombosis, misplacement, or IVC perforation occurred. Recurrent PE was suspected in one of the five patients with IVC/IV thrombosis. Overall mortality was 42.3% (66 patients), and 30-day mortality was 13.5% (21 patients: 10 TrapEase, 11 Greenfield). The study was initially designed to recruit 360 patients in both TrapEase and Greenfield filters in 2 years to demonstrate any statistical significance but was prematurely concluded due to the interim results. CONCLUSION: A higher rate of symptomatic IVC/IV thrombosis is associated with TrapEase filter placement. However, the TrapEase filter still has a selective clinical role in the prevention of thromboembolism in selected patients who are coagulopathic. This is the first randomized prospective study comparing IVC filters since their inception in 1967.