Vascular smooth muscle cells direct extracellular dysregulation in aortic stiffening of hypertensive rats

Aortic stiffening is an independent risk factor that underlies cardiovascular morbidity in the elderly. We have previously shown that intrinsic mechanical properties of vascular smooth muscle cells (VSMCs) play a key role in aortic stiffening in both aging and hypertension. Here, we test the hypothesis that VSMCs also contribute to aortic stiffening through their extracellular effects. Aortic stiffening was confirmed in spontaneously hypertensive rats (SHRs) vs. Wistar‐Kyoto (WKY) rats in vivo by echocardiography and ex vivo by isometric force measurements in isolated de‐endothelized aortic vessel segments. Vascular smooth muscle cells were isolated from thoracic aorta and embedded in a collagen I matrix in an in vitro 3D model to form reconstituted vessels. Reconstituted vessel segments made with SHR VSMCs were significantly stiffer than vessels made with WKY VSMCs. SHR VSMCs in the reconstituted vessels exhibited different morphologies and diminished adaptability to stretch compared to WKY VSMCs, implying dual effects on both static and dynamic stiffness. SHR VSMCs increased the synthesis of collagen and induced collagen fibril disorganization in reconstituted vessels. Mechanistically, compared to WKY VSMCs, SHR VSMCs exhibited an increase in the levels of active integrin β1‐ and bone morphogenetic protein 1 (BMP1)‐mediated proteolytic cleavage of lysyl oxidase (LOX). These VSMC‐induced alterations in the SHR were attenuated by an inhibitor of serum response factor (SRF)/myocardin. Therefore, SHR VSMCs exhibit extracellular dysregulation through modulating integrin β1 and BMP1/LOX via SRF/myocardin signaling in aortic stiffening.     

Plasma N-glycome composition associates with chronic low back pain

Background

Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease.

Decavanadate possesses α-adrenergic agonist activity and a structural motif common with trans-β form of noradrenaline

Decavanadate, an inorganic polymer of vanadate, produced contraction of rat aortic rings at a relatively high concentration compared to phenylephrine, an agonist of -adrenergic receptor. This effect was blocked by two known a-adrenergic receptor antagonists, prazosin and phenoxybenzamine. Decavanadate, formed by possible dimerization of V5 under acid conditions, possessed a structural feature of two pairs of unshared oxygen atoms at a distance of 3.12 Å, not found in its constituents of V4 or V5. A structural motif of O..O..O using such oxygen atoms is recognized in decavanadate. This matches with a similar motif of N..O..O that uses the essential amino and hydroxyl groups of the side-chain and the m-hydroxyl group in trans-b form of noradrenaline. The interaction of such a structural motif with the membrane receptor is likely to be the basis of the unusual noradrenaline-mimic action of decavanadate.     

Spontaneous anaplastic large cell lymphoma in a chimpanzee: A clinicopathological and immunohistochemical study

Abstract: An anaplastic large cell lymphoma with disseminated abdominal metastases was diagnosed in a 35-year-old male chimpanzee. Clinically, the animal displayed lethargy, weight loss, ascites, and abdominal distention. Imaging studies showed several large abdominal masses. At necropsy, variably sized masses of neoplastic mesenteric lymph nodes that encompassed several intestinal loops were present throughout the abdomen. The largest mass measured 9 × 5 cm and had cauliflower-like protrusions into the jejunal lumen. The entire abdominal cavity was covered by a sheet of neoplastic tissue. Histopathologically, the tumor consisted of solid sheets of proliferating lymphoid cells forming a cohesive growth that filled the lymph node sinuses. The tumor had invaded the intestinal wall. Anaplastic large cell lymphoma was diagnosed from immunohistochemistry findings on the basis of positive reaction to the CD3 and CD30 markers and negative reaction to the CD20 marker. Serologic analysis revealed positive titers for Epstein-Barr, cytomegalo-, and varicella-zoster viruses. Both serologic and virologic studies showed no evidence of detectable retroviral infection. This type of tumor has not been reported before in the chimpanzee.     

Differential recognition of MHC class I molecules of xeno-/allo-endothelial cells by human NK cells

Using human umbilical vein endothelial cells (HUVEC) and porcine aortic endothelial cells (PAEC) as target cells, human peripheral blood NK cells (PBNK) and NK92 cells as effector cells, the differential cytotoxicities of NK cells to allo- and xeno-endothelial cells were studied. The influence of MHC class I molecules on the cytotoxicity of human NK cells was assayed using acid treatment, and blockades of MHC class I antigens, CD94 and KIR (NKB1). The results indicated that the killing of PAEC by the two kinds of NK cells is higher than that of HUVEC. After acid- treatment, the cytotoxicity of the two kinds of NK cells to PAEC and HUVEC is significantly enhanced, but the magnitude of the enhancement is different. The enhancement of NK killing to acid treated HUVEC is much greater than that to PAEC. Blockade of CD94 mAb did not alter the NK cytotoxicity, while blockade of NKB1 mAb enhanced the cytotoxicity of PBNK to HUVEC and PAEC by 95% and 29% respectively. The results above suggested that the differential recognition of MHC I molecules of xeno-endothelial cells by human NK cells could be the major reason for higher NK cytotoxicity to PAEC. KIR might be the primary molecule that transduced inhibitory signals when endothelial cells were injured by NK cells.     

Imaging mass spectroscopy delineates the thinned and thickened walls of intracranial aneurysms

Object

The wall thickness of intracranial aneurysms (IAs) is heterogeneous. Although thinning of the IA wall is thought to contribute to IA rupture, the underlying mechanism remains poorly understood. Recently, imaging mass spectroscopy (IMS) has been used to reveal the distribution of phospholipids in vascular diseases. To investigate the feature of phospholipid composition of IA walls, we conducted IMS in a rat model of experimentally induced IA.

Abdominal Adiposity in Six Populations of West African Descent: Prevalence and Population Attributable Fraction of Hypertension

OKOSUN, IKE S., TERRENCE E. FORRESTER, CHARLES N. ROTIMI, BABATUNDE O. OSOTIMEHIN, WALINJOM F. MUNA, AND RICHARD S. COOPER. Abdominal adiposity in six populations of West African descent: prevalence and population attributable fraction of hypertension. Obes Res. Objectives: The objective of this investigation was to examine the prevalence of abdominal adiposity and its association with the prevalence of hypertension among African descent populations in Nigeria, Cameroon, Jamaica, St. Lucia, Barbados, and the United States (US). Research Method: The data for this investigation were obtained from the International Collaborative Study on Hypertension in Blacks. Hypertension was defined as mean diastolic blood pressure ≥90 mmHg, systolic blood pressure ≥140 mmHg or current treatment with prescribed anti-hypertension medication. Abdominal overweight was defined as waist circumference (WC) ≥94 and ≥80 cm for men and women, respectively. Abdominal obesity was defined as WC ≥102 and ≥88 cm for men and women, respectively. We estimated the site-specific prevalence of abdominal overweight and obesity across age and body mass index cut-points. We also calculated the population attributable fraction (AF) of hypertension due to abdominal adiposity. Results: The prevalence of hypertension in these populations was tightly linked to abdominal adiposity. Increases in abdominal overweight accompanied an increasing degree of Westernization, rising from 6. 4% and 26. 3% in Nigeria, 16. 5% and 62. 8% in Cameroon, 15. 8% and 58. 6% in Jamaica, 14. 3% and 62. 1% in St. Lucia, 21. 4% and 70. 3% in Barbados to 38. 9%, and 76. 4% in the US for men and women, respectively. The corresponding values for abdominal obesity were 1. 6% and 12. 3% in Nigeria, 5. 1% and 38. 9% in Cameroon, 5. 5% and 34. 0% in Jamaica, 2. 7% and 40. 7% in St. Lucia, 7. 8% and 44. 7% in Barbados to 21. 7% and 54. 1% in the US for men and women, respectively. Body mass index-adjusted estimates of AF suggest that in most of these populations, especially in females, avoidance of abdominal overweight or obesity would help to curb the development of hypertension. Discussion: An important public health challenge is to clarify how lifestyle factors influence risks of abdominal adiposity and ultimately the increased risk of cardiovascular diseases.     

Sphingosine 1-Phosphate Regulates Heat Shock Protein 27 Induction by a p38 MAP Kinase-Dependent Mechanism in Aortic Smooth Muscle Cells

In an aortic smooth muscle cell line, A10 cells, we investigated the effect of sphingosine 1-phosphate on the induction of heat shock protein 27 (HSP27), a low-molecular-weight heat shock protein. Sphingosine 1-phosphate significantly induced the accumulation of HSP27 in a pertussis toxin-sensitive manner. The effect was dose-dependent in the range between 0.1 and 30 microM. Sphingosine 1-phosphate stimulated an increase in the levels of mRNA for HSP27. Sphingosine 1-phosphate stimulated both p42/p44 mitogen-activated protein (MAP) kinase and p38 MAP kinase activation. PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase, did not affect sphingosine 1-phosphate-stimulated HSP27 induction. In contrast, SB203580, an inhibitor of p38 MAP kinase, reduced sphingosine 1-phosphate-induced HSP27 induction. SB203580 reduced the levels of mRNA for HSP27 induced by sphingosine 1-phosphate. These results indicate that sphingosine 1-phosphate stimulates the induction of HSP27 via p38 MAP kinase activation in aortic smooth muscle cells.