Platelet and monocyte activity markers and mediators of inflammation in Takotsubo cardiomyopathy.

Patients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- and monocyte-activity markers in patients with TC and MI for significant differences. Clinical data of patients with TC (n = 16) and acute MI (n = 16) were obtained. Serial blood samples were taken at the time of hospital admission (t(0)), after 2-4 days (t(1)) and after 4-7 weeks (t(2)), respectively. Plasma concentrations of interleukin (IL)-6, IL-7, soluble CD40 ligand (sCD40L), and monocyte chemotactic protein 1 (MCP-1) were determined with an ELISA. Tissue factor binding on monocytes, platelet-activation marker CD62P, platelet CD40-ligand (CD40L), and platelet-monocyte aggregates were measured using flow cytometry. Expression of CD62P on platelets and IL-6 plasma levels were significantly lower in patients with TC compared to MI at the time of hospital admission. IL-7 plasma levels were significantly elevated in patients with TC compared to patients with MI at 2-4 days after hospital admission. No significant differences were observed concerning sCD40L and MCP-1 plasma levels, tissue factor binding on monocytes, CD40L expression on platelets, and platelet-monocyte aggregates at any point in time. Our results indicate that inflammatory mediators and platelet-activity markers contribute to the differences in the pathogenesis of MI and TC.

Concerted action of androgens and mechanical strain shifts bone metabolism from high turnover into an osteoanabolic mode.

Adhesion of bone cells to the extracellular matrix is a crucial requirement for osteoblastic development and function. Adhesion receptors connect the extracellular matrix with the cyto-skeleton and convey matrix deformation into the cell. We tested the hypothesis that sex hormones modulate mechanoperception of human osteoblastic cells (HOB) by affecting expression of adhesion molecules like fibronectin and the fibronectin receptor. Only dihydrotestosterone (DHT), but not 17beta-estradiol, stimulated fibronectin (137%) and fibronectin receptor (252%) protein expression. The effects of deformation strain on HOB metabolism were investigated in a FlexerCell strain unit. Cyclically applied strain (2.5% elongation) increased DNA synthesis (125%) and interleukin-6 (IL-6) production (170%) without significantly affecting alkaline phosphatase (AP) activity, type I collagen (PICP), or osteoprotegerin (OPG) secretion. 10 nM DHT pretreatment abolished the mitogenic response of HOB to strain and increased AP activity (119%), PICP (163%), and OPG production (204%). In conclusion, mechanical strain stimulates bone remodeling by increasing HOB mitosis and IL-6 production. DHT enhances the osteoanabolic impact of deformation strain by increasing bone formation via increased AP activity and PICP production. At the same time, bone resorption is inhibited by decreased IL-6 and increased OPG secretion into the bone microenvironment.

[Osteoporosis and cardiovascular disease--two sides of the same coin?]. / Osteoporose und koronare Herzkrankheit--zwei Seiten der gleichen Münze?

BACKGROUND: Osteoporosis and cardiovascular disease have numerous epidemiologic changes, health economic consequences, and molecular mechanisms in common, which are highlighted in this short review. EPIDEMIOLOGY AND CLINICAL STUDIES: The incidence of osteoporosis and cardiovascular disease is increasing in western societies, and genetic background, nutrition and psychologic factors play important roles in the pathogenesis of both diseases. The presence of a decreased bone mass or osteoporotic vertebral fractures are associated with an increased cardiovascular mortality. Calcaneal bone loss of 1 SD (standard deviation) as measured by osteodensitometry is associated with a 1.31 times increased risk for the occurrence of stroke. MOLECULAR MECHANISMS: The observed increase in interleukin-6 and tumor necrosis factor serum concentrations during the menopause contributes to osteoporotic bone loss and is associated with arteriosclerosis. Furthermore, the presence of hydroxyapatite in arteriosclerotic plaques supports the notion of common pathogenetic mechanisms for both, osteoporosis and arteriosclerosis. Osteopontin, bone GLA protein and bone morphogenetic protein-2, which have first been isolated from the organic bone matrix, are also present in arteriosclerotic plaques. 1,25-dihydroxycholecalciferol potently stimulates bone matrix mineralization and is also a negative regulator of the renin-angiotensin system; therefore vitamin D(3) deficiency in addition to bone metabolism also affects blood pressure. Osteoporosis and arteriosclerosis develop in mice lacking the osteoprotegerin gene and also in klotho gene knockout mice. CONCLUSION: Diagnosis of osteopenia, osteoporosis and osteoporotic vertebral or hip fractures indicates the presence of an increased cardiovascular risk which needs to be addressed by the physician who cares for patients with osteoporosis. The experimental finding of an osteoanabolic effect of statins supports the possibility of common pathogenetic disturbances which may be responsible for the simultaneous and frequent manifestation of osteoporosis and arteriosclerosis in elderly patients.