Atherosclerosis, the underlying cause of coronary artery disease (CAD), has a significant inflammatory component. White blood cell count is an affordable and accessible way to assess the systemic ...immune response, as it comprises many subgroups with distinct and complex functions. Considering their multidirectional effect on atherosclerosis, new biomarkers integrating various leukocyte subgroups, the Systemic Inflammatory Index (SII) and the Systemic Inflammatory Response Index (SIRI), were recently devised to describe the balance between inflammation and immune reaction. This research aimed to evaluate the relationship of the intensity of inflammation measured by these biomarkers with the severity of CAD assessed with coronary angiography and with the diagnosis of acute coronary syndrome (ACS) or stable CAD in 699 patients. SIRI, but not SII, was associated with the diagnosis, having the highest values for patients with ACS (STEMI), significantly higher than in patients with stable CAD (p < 0.01). The highest SII and SIRI values were observed in patients with three-vessel CAD. SII and SIRI require further in-depth and well-designed research to evaluate their potential in a clinical setting.
Cell death in human diseases is often a consequence of disrupted cellular homeostasis. If cell death is prevented without restoring cellular homeostasis, it may lead to a persistent dysfunctional and ...pathological state. Although mechanisms of cell death have been thoroughly investigated
, it remains unclear how homeostasis can be restored after inhibition of cell death. Here we identify TRADD
, an adaptor protein, as a direct regulator of both cellular homeostasis and apoptosis. TRADD modulates cellular homeostasis by inhibiting K63-linked ubiquitination of beclin 1 mediated by TRAF2, cIAP1 and cIAP2, thereby reducing autophagy. TRADD deficiency inhibits RIPK1-dependent extrinsic apoptosis and proteasomal stress-induced intrinsic apoptosis. We also show that the small molecules ICCB-19 and Apt-1 bind to a pocket on the N-terminal TRAF2-binding domain of TRADD (TRADD-N), which interacts with the C-terminal domain (TRADD-C) and TRAF2 to modulate the ubiquitination of RIPK1 and beclin 1. Inhibition of TRADD by ICCB-19 or Apt-1 blocks apoptosis and restores cellular homeostasis by activating autophagy in cells with accumulated mutant tau, α-synuclein, or huntingtin. Treatment with Apt-1 restored proteostasis and inhibited cell death in a mouse model of proteinopathy induced by mutant tau(P301S). We conclude that pharmacological targeting of TRADD may represent a promising strategy for inhibiting cell death and restoring homeostasis to treat human diseases.
The incidence of ischemic heart disease (IHD) increases every year. This cardiovascular disease has an inflammatory factor in its etiology due to different immune cells that influence atherogenesis. ...New inflammatory biomarkers—the Systemic Inflammatory Index (SII) and the Systemic Inflammatory Response (SIRI)—attempt to describe the pro- and anti-inflammatory balance and quantify the complex impact of the immune system on atherosclerosis, while vitamin D has a multidirectional impact on the human body, including the cardiovascular and immune systems. Hence, the objective of this research was to analyze the association between SII and SIRI and serum vitamin D concentrations in patients with IHD. A significant correlation was observed between SIRI and 25(OH)D in the whole group and between both biomarkers (SII and SIRI) and 25(OH)D in the group of patients with ACS but not in the group of patients with stable IHD. The role of vitamin D in IHD complications and its association with new inflammatory biomarkers requires further well-designed, large-scale research.
Cardiovascular disease (CVD) continues to be the leading cause of death in European men. Atherosclerosis and its clinical consequence, chronic coronary syndrome (CCS), comprise two main elements: ...dysfunction of lipoprotein metabolism and an important inflammatory component that contributes to the development of complications, including acute coronary syndrome (ACS). Measures of both components are combined in a composite marker called monocyte-to-HDL ratio (MHR). Vitamin D was previously described to influence inflammation processes, and its deficiency influences CVD risk factors. This research describes the differences in MHR and total serum 25-hydroxyvitamin D (25(OH)D) concentration between male patients with different diagnoses of CCS and the correlation between 25(OH)D and MHR in this group. Significant differences were observed between ACS and CCS patients in 25(OH)D and MHR—the highest HDL and serum 25(OH)D concentrations were observed in patients with CCS, whereas the highest value of MHR was observed in patients with STEMI. A significant correlation was observed between 25(OH)D, HDL, and MHR. Due to the significant but small nominal difference in MHR values between groups of patients diagnosed with ACS and CCS, and the possible influence of age and hyperlipidemia status on the differences in vitamin D levels in these groups, this subject requires further well-designed research. The suggested bidirectional relationship between MHR and 25(OH)D and the role of MHR as a predictor of vitamin D status in the body also needs to be verified.
Coronary artery disease (CAD) in women occurs later than in men. Underlying atherosclerosis, a chronic process of lipoprotein deposition in arterial walls with a prominent inflammatory component, is ...influenced by several risk factors. In women, commonly used inflammatory markers are generally found to be related to the occurrence of acute coronary syndrome (ACS), as well as the development of other diseases that influence CAD. New inflammatory markers derived from total blood count-systemic inflammatory response index (SII), systemic inflammatory reaction index (SIRI), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR)-were analyzed in the group of 244 elderly, postmenopausal women with the diagnosis of ACS or stable CAD. SII, SIRI, MLR, and NLR were significantly higher in women with ACS compared to those with stable CAD (
< 0.05 for all)-the highest values were observed in women with NSTEMI. MLR from new inflammatory markers, HDL, and history of MI turned out to be significant factors associated with ACS. These results suggest that MLR as representative of blood count-derived inflammatory markers may be considered as additional CVD risk factors in women with suspected ACS.
Coronary artery disease (CAD), the leading cause of death worldwide, has an underlying cause in atherosclerosis. The activity of this inflammatory process can be measured with ...neutrophil-to-lymphocyte ratio (NLR). The anti-inflammatory and anti-atherogenic properties of vitamin D affect many mechanisms involved in CAD. In this study, we investigated the association between NLR, vitamin D concentration, and severity of CAD in a group of patients with a history of myocardial infarction (MI). NLR was higher in patients with acute coronary syndrome (ACS) in comparison to those with stable CAD (median: 2.8, range: 0.96−24.3 vs. median: 2.3, range: 0.03−31.6; p < 0.05). No associations between NLR and severity of CAD (p = 0.14) in the cohort and in the subgroups with stable CAD (p = 0.40) and ACS (p = 0.34) were observed. We found no correlation between vitamin D level and NLR neither in the whole study group (p = 0.29) nor in subgroups of patients with stable CAD (p = 0.84) and ACS (p = 0.30). NLR could be used as prognostic biomarker of consecutive MI in patients with CAD and a history of MI.
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