Chemerin and CMKLR1 expression in human arteries and periadventitial fat: a possible role for local chemerin in atherosclerosis?

BACKGROUND: Depending on their anatomical location, different fat depots have a different capacity to produce bioactive peptides, called adipokines. Adipokines produced by periadventitial fat have been implicated in the pathogenesis of vascular disease, including atherosclerosis. Chemerin is an adipokine with an established role in immunity, adipose tissue function and metabolism, acting in autocrine, paracrine and endocrine manners. We investigated the protein expression of chemerin and its receptor, CMKLR1, in human aortas, coronary vessels and the respective periadventitial adipose tissue and correlated their expression with the presence of atherosclerosis. METHODS: Immunohistochemistry for chemerin and CMKLR1 was performed on human aortic and coronary artery samples including the periadventitial adipose tissue. Aortic and coronary atherosclerotic lesions were assessed using the AHA classification. RESULTS: Chemerin immunopositivity was noticed in both periadventitial fat depots, in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Periadventitial fat and foam cell chemerin immunopositivity was statistically significantly correlated with the severity of atherosclerosis in both locations. CMKLR1 was expressed in vascular smooth muscle cells and foam cells in aortic and coronary vessels with atherosclerotic lesions. CMKLR1 immunostaining in foam cells was statistically significantly correlated with aortic atherosclerosis. CONCLUSIONS: Our results lend some support to a presumable role of locally produced chemerin in the progression of atherosclerotic lesions, possibly acting through its CMKLR1 receptor. Further research will elucidate the role of chemerin signaling in atherosclerosis.

Adiponectin/T-cadherin and apelin/APJ expression in human arteries and periadventitial fat: implication of local adipokine signaling in atherosclerosis?

INTRODUCTION: Adipose tissue is considered an endocrine organ, producing bioactive peptides, called adipokines. Adipokines produced by periadventitial fat have been implicated in the pathogenesis of vascular disease, including atherosclerosis. Adiponectin has established antiatherogenic actions, while the role of T-cadherin as an adiponectin receptor is not fully elucidated. The apelinergic system, consisting of apelin and its APJ receptor, is a mediator of various cardiovascular functions and may also be involved in the atherosclerotic process. We investigated the protein expression of adiponectin, T-cadherin, apelin and APJ in human aortas, coronary vessels, and the respective periadventitial adipose tissue and correlated their expression with the presence of atherosclerosis and clinical parameters. METHODS: Immunohistochemistry for adiponectin, T-cadherin, apelin, and APJ was performed on human aortic and coronary artery samples including the periadventitial adipose tissue. Aortic and coronary atherosclerotic lesions were assessed using the american heart association (AHA) classification. RESULTS: Adiponectin immunostaining, of varied intensity, was detected only in adipocytes, while T-cadherin was localized to vascular smooth muscle cells (VSMCs) and endothelial cells. Apelin immunostaining was detected in adipocytes, VSMCs, endothelial cells, and foam cells in atherosclerotic lesions, while APJ was found in VSMCs and endothelia. Periadventitial adiponectin and VSMC T-cadherin expression were negatively correlated with atherosclerosis in both sites, as was VSMC apelin expression. Several other - depot specific - associations were observed. CONCLUSIONS: Our results suggest a possible role for T-cadherin as a mediator of antiatherogenic adiponectin actions, while they support the putative antiatherogenic profile for apelin and its APJ receptor in human arteries. Further research is absolutely necessary to confirm these notions. SUMMARY: Periadventitial adipose tissue adipokines are implicated in vascular physiology and pathology. Adiponectin/T-cadherin and apelin/APJ immunoreactivity is detected in human aortas and coronary arteries. Adiponectin/T-cadherin and apelin/APJ expression patterns were found to be inversely associated with human aortic and coronary atherosclerosis.

Adipokines in periaortic and epicardial adipose tissue: differential expression and relation to atherosclerosis.

AIM: Adipokines are protein products of adipose tissue with paracrine and endocrine actions, which have been implicated in the pathogenesis of cardiovascular disease. Locally produced adipokines, especially by periadventitial adipose tissue, may affect vascular physiology and pathology. We investigated the expression of adiponectin, visfatin, leptin and novel adipokines chemerin and vaspin in human periaortic and epicardial adipose tissue, as well as their correlation to aortic and coronary atherosclerosis. METHODS: Standard immunohistochemical staining for the adipokines was performed on samples of human periaortic, pericoronary and apical epicardial adipose tissue. Atherosclerotic lesions of the adjacent vascular wall were assessed using the AHA classification. RESULTS: Adipokines were expressed in periadventitial and apical epicardial adipose tissue and - except for adiponectin - in vascular smooth muscle cells and foam cells in atherosclerotic lesions. Aortic atherosclerosis was positively correlated with chemerin, vaspin, visfatin and leptin periaortic fat expression. Coronary atherosclerosis was positively correlated with chemerin and visfatin pericoronary fat expression. Adipose tissue adiponectin expression was negatively correlated to atherosclerosis in both locations. Expression of adipokines in apical epicardial fat was not associated with atherosclerosis. CONCLUSIONS: Our results show: a) a different expression pattern of adiponectin, visfatin, leptin, chemerin and vaspin in periaortic, pericoronary and apical epicardial adipose tissue, b) a correlation of these adipokines with either aortic or coronary atherosclerosis or both in a pattern characteristic for each adipokine and suggest that locally produced adipokines might differently affect the atherosclerotic process in different locations.

Estrogen signaling in colorectal carcinoma microenvironment: expression of ERbeta1, AIB-1, and TIF-2 is upregulated in cancer-associated myofibroblasts and correlates with disease progression.

Epidemiological and molecular data suggest the involvement of estrogen signaling in colorectal tissue, mediated mainly through estrogen receptor beta (ERbeta). Estrogens may mediate their effects in epithelial cells indirectly by acting on stromal cells. Expression of ERalpha, ERbeta1, and the ER coregulators, amplified in breast cancer-1 (AIB-1) and transcriptional intermediary factor 2 (TIF-2), was evaluated in myofibroblasts of 107 colorectal carcinomas, 77 paired samples of normal mucosa, and 29 adenomas by immunohistochemistry. Double immunostaining with a-SMA was used to identify the myofibroblasts of normal tissue, adenomas, and cancer microenvironment. ERalpha was not expressed in stromal cells. Nuclear expression of ERbeta1, AIB-1, and TIF-2 in myofibroblasts gradually increased from normal mucosa, through adenomas, to carcinomas. Cytoplasmic ERbeta1 and TIF-2 expression was enhanced in carcinomas compared to normal mucosa and adenomas. Enhanced nuclear and cytoplasmic ERbeta1 expression and elevated nuclear AIB-1 expression were more frequently noted in myofibroblasts of carcinomas of advanced stage. ERbeta1 expression in cancer-associated myofibroblasts correlated to AIB-1 and TIF-2 expression. None of the markers correlated with patients' prognosis. Our findings imply that ERbeta1-dependent (genomic and non-genomic) and ER-coregulator-dependent (AIB-1, TIF-2) signal transductions in myofibroblasts may be involved in the initiation and progression of colorectal carcinomas.

Expression of estrogen receptor co-regulators NCoR and PELP1 in epithelial cells and myofibroblasts of colorectal carcinomas: cytoplasmic translocation of NCoR in epithelial cells correlates with better [corrected] prognosis.

Proline-, glutamic acid-, and leukine-rich protein (PELP1) is a novel co-regulatory protein that modulates genomic and non genomic actions of estrogen receptors. Nuclear receptor co-repressor (NCoR) represses estrogen-receptor-dependent transcription. PELP1 and NCoR expression was evaluated in tissue sections from 107 formalin-fixed, paraffin-embedded colectomy specimens. Normal mucosa and adenomas were also evaluated in 77 and 29 cases, respectively. PELP1 was expressed in a dot-like pattern in the nuclei of epithelial and stromal cells. Statistical analysis revealed an increase in PELP1 expression in myofibroblasts from normal mucosa through adenomas to carcinomas. NCoR was expressed in the nuclei and the cytoplasm of epithelial cells. Nuclear expression was more common in normal mucosa, whereas cytoplasmic expression was higher in malignant epithelial cells. Additionally, NCoR was expressed in the cytoplasm of cancer-associated myofibroblasts, but was rarely noted in myofibroblasts of normal mucosa or adenomas. Cytoplasmic expression of NCoR in epithelial cells correlated with better disease-free and overall survival on univariate analysis and was an independent prognostic marker for disease-free survival on multivariate analysis. These findings suggest that deregulation of co-regulators expression in both epithelial cells and myofibroblasts may contribute to the initiation and progression of colorectal carcinoma.

Expression of adiponectin and adiponectin receptors in human pituitary gland and brain.

BACKGROUND/AIMS: Adiponectin and its receptors, AdipoR1 and AdipoR2, constitute integral components of energy homeostatic mechanism in peripheral tissues. Recent studies have implicated adiponectin in central neural networks regulating food intake and energy expenditure. The present study aimed at investigating the possible expression and distribution of adiponectin and its receptors in human pituitary gland, hypothalamus and different brain areas. METHODS: Sections of the pituitary gland, hypothalamus and adjacent basal forebrain area, cerebrum and cerebellum from 35 autopsy cases, were examined using HE, PAS-Orange G, luxol fast blue/cresyl violet stains and single and double immunohistochemistry using adiponectin, AdipoR1, AdipoR2, choline acetyltransferase, FSH, LH, TSH, GH, ACTH and prolactin-specific antibodies. Age and BMI mean values +/- SD of the autopsy cases were 56 +/- 18 years and 27 +/- 5 kg/m(2), respectively. RESULTS: Strong adiponectin expression was observed in pituitary gland. In pars distalis (PD), adiponectin localized in GH, FSH, LH and TSH-producing cells and in pars tuberalis (PT) in FSH, LH and TSH-producing cells. Strong to moderate expression of AdipoR1 and AdipoR2 was observed in PD by the same cell types as adiponectin. No immunoreactivity for adiponectin receptors was noted in cells of PT. Intense AdipoR1 immunostaining was observed in neurons of lateral hypothalamic area and of nucleus basalis of Meynert (NBM). CONCLUSIONS: Adiponectin and its receptors expression in human pituitary might indicate the existence of a local system, modulating endocrine axes. Furthermore, the presence of AdipoR1 in hypothalamus and NBM suggests that adiponectin may participate in central neural signaling pathways controlling energy homeostasis and higher brain functions.

Modal damping for monitoring bone integrity and osteoporosis.

We applied a noninvasive method to assess bone structural integrity. The method is based on the measurement of the dynamic characteristics of the bone (quality factor and modal damping factor) by applying vibration excitation in the range of acoustic frequencies, in the form of an acoustic sweep signal. Excised sheep femora were tested to detect changes in modal damping, density (kg/m3), bone mineral density (kg/m2) and bone mineral (hydroxyapatite) percentage. The changes were recorded after each time of chemical treatment of the bones performed to gradually cause mineral removal, thus simulating osteoporosis. It was shown that the change in quality factor and damping was in all cases on average equal or greater to the change in all other measured characteristics, thus strengthening the potential of the proposed method to become a valuable assessment tool for monitoring bone integrity and osteoporosis.