The Role of Costimulatory Receptors of the Tumour Necrosis Factor Receptor Family in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease that is mediated by both the innate and adaptive immune responses. T lymphocytes, that together with B cells are the cellular effectors of the adaptive immune system, are currently endowed with crucial roles in the development and progression of atherosclerosis. Costimulatory receptors are a class of molecules expressed by T lymphocytes that regulate the activation of T cells and the generation of effector T-cell responses. In this review we present the roles of costimulatory receptors of the tumour necrosis factor receptor (TNFR) superfamily in atherosclerosis and discuss the implications for future therapies that could be used to specifically modulate the immune response of pathogenic T cells in this disease

Truncated human endothelin receptor A produced by alternative splicing and its expression in melanoma

In this study, reverse transcriptase polymerase chain reaction was used to amplify human endothelin receptor A (ETA) and ETB receptor mRNA. A truncated ETA receptor transcript with exons 3 and 4 skipped was found. The skipping of these two exons results in 109 amino acids being deleted from the receptor. The truncated receptor was expressed in all tissues and cells examined, but the level of expression varied. In melanoma cell lines and melanoma tissues, the truncated receptor gene was the major species, whereas the wild-type ETA was predominant in other tissues. A 1.9-kb ETA transcript was identified in melanoma cell lines by Northern blot, which was much smaller than the transcript in heart and in other tissues reported previously (4.3 kb). The cDNA coding regions of the truncated and wild-type ETA receptors were stably transfected into Chinese hamster ovary (CHO) cells. The truncated ETA receptor-transfected CHO cells did not show binding affinity to endothelin 1 (ET-1) or endothelin 3 (ET-3). The function and biological significance of this truncated ETA receptor is not clear, but it may have regulatory roles for cell responses to ETs

Progression of endothelial dysfunction, atherosclerosis, and arterial stiffness in stable kidney transplant patients: a pilot study.

BACKGROUND: Kidney transplant patients suffer from vascular abnormalities and high cardiovascular event rates, despite initial improvements post-transplantation. The nature of the progression of vascular abnormalities in the longer term is unknown. This pilot study investigated changes in vascular abnormalities over time in stable kidney transplant patients long after transplantation. METHODS: Brachial artery flow-mediated dilation (FMD), nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cf-PWV), ankle-brachial pressure index, and common carotid artery intima-media thickness (CCA-IMT) were assessed in 18 kidney transplant patients and 17 controls at baseline and 3-6 months after. RESULTS: There was no difference in age (51 ± 13 vs. 46 ± 11; P = 0.19), body mass index (26 ± 5 vs. 25 ± 3; P = 0.49), serum cholesterol (4.54 ± 0.96 vs. 5.14 ± 1.13; P = 0.10), systolic blood pressure (BP) (132 ± 12 vs. 126 ± 12; P = 0.13), diastolic BP (82 ± 9 vs. 77 ± 8; P = 0.10), or diabetes status (3 vs. 0; P = 0.08) between transplant patients and controls. No difference existed in vascular markers between patients and controls at baseline. In transplant patients, FMD decreased (- 1.52 ± 2.74; P = 0.03), cf-PWV increased (0.62 ± 1.06; P = 0.03), and CCA-IMT increased (0.35 ± 0.53; P = 0.02). No changes were observed in controls. CONCLUSION: Markers of vascular structure and function worsen in the post-transplant period on long-term follow-up, which may explain the continued high cardiovascular event rates in this population

Ethnic and Regional Differences in the Management of Angina: The Way Forward.

For decades, there has been great interest in ethnic differences in the management of angina and stable cardiovascular disease. Clinical decisionmaking is known to be both consciously and unconsciously influenced by a patient's demographics, and this is due to in part to differences in clinical guidance and opinion. However, the evidence supporting such decision-making is sparse. Nonetheless, there is overwhelming evidence that international, national, regional, institutional, departmental and individual bias disproportionately affect subgroups of the population, resulting in adverse patient outcomes. While without doubt there will be rapid advancements in individualised therapies over the coming years and decades, the most beneficial immediate action clinicians can take is to reduce disparities in both the evidence base and care provision. Doing so will require great collaborative effort

Small Vessel Disease in the Heart and Brain: Current Knowledge, Unmet Therapeutic Need and Future Directions

No abstract available

Targeting T cells to treat atherosclerosis: Odyssey from bench to bedside

More than 150 years from the initial description of inflammation in atherosclerotic plaques, randomized clinical trials to test anti-inflammatory therapies in atherosclerosis have recently been initiated. Lymphocytes and macrophages are main participants in the inflammatory response in atherosclerosis. T lymphocytes operate mainly by exerting strong influences on the function of many cells in the immune system and beyond, and co-ordinating their interactions. Importantly, T lymphocytes are not a homogenous population, but include several subsets with specialized functions that can either promote or suppress inflammation. The interactions between these T-lymphocyte subsets have critical consequences on the course and outcome of inflammation. The complexity of the inflammatory response in atherosclerosis poses significant challenges on translating experimental findings into clinical therapies and makes the journey from bench to bedside an arduous one. Here, we summarize recent advances on the role of CD4 + T cells in the inflammatory process in atherosclerosis and discuss potential therapies to modulate these lymphocytes that may provide future breakthroughs in the treatment of atherosclerosis