TRPA1 as a promising target in ischemia/reperfusion: A comprehensive review.

Ischemic disorders, including myocardial infarction, cerebral ischemia, and peripheral vascular impairment, are the main common reasons for debilitating diseases and death in Western cultures. Ischemia occurs when blood circulation is reduced in tissues. Reperfusion, although commanded to return oxygen to ischemic tissues, generates paradoxical tissue responses. The responses include generating reactive oxygen species (ROS), stimulating inflammatory responses in ischemic organs, endoplasmic reticulum stress, and the expansion of postischemic capillary no-reflow, which intensifies organ damage. Multiple pathologic processes contribute to ischemia/reperfusion; therefore, targeting different pathologic processes may yield an effective therapeutic approach. Transient Receptor Potential A1 (TRPA1) belongs to the TRP family of ion channels, detects a broad range of chemicals, and promotes the transduction of noxious stimuli, e.g., methylglyoxal, ROS, and acrolein effects are attributed to the channel's sensitivity to intracellular calcium elevation or phosphoinositol phosphate modulation. Hypoxia and ischemia are associated with oxidative stress, which activates the TRPA1 channel. This review describes the role of TRPA1 and its related mechanisms that contribute to ischemia/reperfusion. Relevant articles were searched from PubMed, Scopus, Web of Sciences, and Google Scholar electronic databases, up to the end of August 2023. Based on the evidence presented here, TRPA1 may have protective or deteriorative functions during the ischemia/reperfusion process. Its function depends on the activation level, the ischemic region, the extent of lesions, and the duration of ischemia.

Lipid-lowering drugs and cancer: an updated perspective.

Statins and non-statin medications used for the management of dyslipidemia have been shown to possess antitumor properties. Since the use of these drugs has steadily increased over the past decades, more knowledge is required about their relationship with cancer. Lipid-lowering agents are heterogeneous compounds; therefore, it remains to be revealed whether anticancer potential is a class effect or related to them all. Here, we reviewed the literature on the influence of lipid-lowering medications on various types of cancer during development or metastasis. We also elaborated on the underlying mechanisms associated with the anticancer effects of antihyperlipidemic agents by linking the reported in vivo and in vitro studies.

Comparison of the prevalence of enteroviruses in blood samples of patients with and without unstable angina.

BACKGROUND: Although the role of enteroviruses has been proved in heart diseases, extensive information is not available on the association between enteroviruses and unstable angina. In the present study, the authors compared the prevalence of enteroviruses in patients with and without unstable angina. METHODS: Blood samples were taken from 51 patients with unstable angina and 55 patients without unstable angina or myocardial infarction that were admitted to Imam Reza and Ghaem hospitals (Mashhad, northeast of Iran). Reverse transcription polymerase chain reaction (RT-PCR) was performed using specific primers for the detection of the enteroviruses in blood samples of study subjects. RESULTS: Patients with and without unstable angina were similar in age with mean ± standard deviation of 62.6 ± 12.8 and 59.7 ± 12.7 years, respectively (P = 0.243) and there were no differences in gender in these two groups (P = 0.174). Prevalence of the enteroviruses in patients with unstable angina was higher only in 66-80 years age group compared to the control group (patients without unstable angina, P = 0.032). There was a higher prevalence of enterovirus RNA positivity in the blood samples of women with unstable angina (75.9%) than those without unstable angina (41.7%, P = 0.011), however, no significant difference was observed in men (P = 0.983). CONCLUSION: Our data showed that enteroviral RNA positivity was higher in patients with unstable angina compared to those without unstable angina. However, the differences between the two groups were not statistically significant.

Angiotensin II Type 1 Receptor Gene A1166C Polymorphism Was Not Associated With Acute Coronary Syndrome in an Iranian Population.

BACKGROUND: There are very limited data for Iranian populations on the predisposing genetic factors for acute coronary syndrome (ACS). OBJECTIVES: The objective of the present study was to investigate the association of the angiotensin II type 1 receptor (AT1R) gene polymorphism and ACS in an Iranian population. PATIENTS AND METHODS: This cross-sectional study was conducted among 263 subjects (97 men and 166 women). Patients (n = 128) aged 30 - 80 years with chest pain were recruited from the emergency department of Ghaem Hospital (Mashhad, Iran). A 12-lead electrocardiograph plus creatine kinase MB (CK-MB) levels were used as the basis for the diagnosis of myocardial ischemia. The control group was selected from age-matched healthy subjects (n = 135). Non-enzymatic kits were used for extraction of DNA from blood samples. Polymerase chain reaction (PCR) was performed to amplify the DNA fragments. For restriction fragment length polymorphism (RFLP) determination, the DdeI enzyme was used to digest the amplified DNA fragments. Statistical analyses were performed using SPSS version 13.0. RESULTS: There was no statistical difference in the genotype frequency of patients and healthy subjects with regard to age and gender (P > 0.05). CONCLUSIONS: The AT1R A1166C polymorphism appeared not to be associated with the presence of ACS in the population studied.

TNF-alpha Production by Peripheral Blood Monocytes in Multiple Sclerosis Patients and Healthy Controls.

BACKGROUND: Aberrant immune responses are evident in the pathogenesis of multiple sclerosis (MS) and it has been proposed that the spectrum of cytokines influence disease outcomes. Leptin and lipopolysaccharide (LPS) of Gram-negative bacteria are both potent cellular stimulators for production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). The aim of this study was to compare the TNF-α production by peripheral blood monocytes from MS patients with healthy controls. METHODS: Peripheral blood samples were stimulated with LPS or leptin. After blocking the Golgi apparatus, intracellular cytokine production was assessed using a monoclonal antibody against human TNF-α by the flow cytometry technique. Moreover, plasma level measurement of cytokines was performed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Intracellular levels of TNF-α were 16.80 ± 8.21 and 16.52 ± 8.23in MS patients and healthy controls which showed no statistically significant difference between them (p = 0.850). Leptin-stimulated and LPS-stimulated TNF-α production showed no significant difference between MS patients and the control group (p = 0.263 and p = 0.191, respectively). However, after treatment with leptin, a weak significant difference was shown between cases and control group (p = 0.049). There were significant differences between cases and controls regarding serum levels of IL-6 and Toll-like receptor-4 (TLR-4) before and after stimulation with leptin and LPS, separately (p < 0.05). CONCLUSION: Taken together, we cannot definitely conclude that TNF-α does not play an important role in pathogenesis of MS. However, other characteristics of monocyte activation such as IL-6 or TLRs can elucidate implication of peripheral blood monocytes in MS pathogenesis.

Changes in small dense low-density lipoprotein levels following acute coronary syndrome.

Low-density lipoprotein (LDL), especially small dense LDL (sdLDL), plays a role in atherogenesis. We compared baseline sdLDL levels between healthy controls and patients with acute coronary syndrome (ACS). Blood samples were taken from patients diagnosed with myocardial infarction ([MI] n = 104) and unstable angina ([UA] n = 100). Both sdLDL and high-sensitivity C-reactive protein (hsCRP) levels were determined on admission and in the next 24 hours after the onset of symptoms. Baseline concentration of sdLDL was significantly higher in patients presenting with ACS than controls (P < .05). In the 24 hours following ACS, the sdLDL levels decreased insignificantly in both groups of patients with ACS (P > .05). The changes in sdLDL values were not significantly different between MI and UA participants (P > .05). Patients with ACS have higher concentration of sdLDL compared with the controls.

Changes in anti-heat shock protein 27 antibody and C-reactive protein levels following cardiac surgery and their association with cardiac function in patients with cardiovascular disease.

The relationship between serum anti-heat shock protein (Hsp)27 antibody and high sensitive C-reactive protein (hs-CRP) levels and indices of cardiac function were investigated in patients undergoing coronary artery bypass grafting (CABG) or heart valve replacement. The changes in anti-Hsp27 antibody titers and hs-CRP levels were compared among patients undergoing off-pump and on-pump CABG or valvular heart replacement. Fifty-three patients underwent off-pump, on-pump CABG, and heart valvular replacement in each group. Serum anti-Hsp27 titers and hs-CRP values were measured 24 h before and after the operation and at discharge. Echocardiography was performed before surgery and before discharge. The results were compared with values from 83 healthy controls. hs-CRP levels increased and anti-Hsp27 antibody decreased following surgery (P < 0.001 and P < 0.05, respectively), although these changes were independent of operative procedure (P = 0.361 and P = 0.120, respectively). Anti-Hsp27 antibody levels were higher at the time of discharge (P = 0.016). Only in coronary patients were anti-Hsp27 antibody levels negatively associated with E/E' (r = -0.268, P = 0.022), a marker of pulmonary capillary wedge pressure. In conclusions, anti-Hsp27 antibody levels are associated with indices of cardiac function in coronary patients. Cardiopulmonary bypass had no significant effect on the induction of changes in anti-Hsp27 levels. Moreover, anti-Hsp27 antibody levels fell in all groups postoperatively; this may be due to the formation of immune complexes of antigen-antibody, and antibody levels were higher at the time of discharge.

Prooxidant-antioxidant balance and antioxidized LDL antibody level values and cardiac function in patients with coronary artery disease.

OBJECTIVES: We studied the association between the prooxidant-antioxidant balance (PAB), anti-malondialdehyde-modified low-density lipoprotein (oxidized LDL, ox-LDL) IgG antibody and indices of cardiac function (systolic and diastolic function) in patients with coronary artery disease (CAD). METHODS: Fifty-five patients with established CAD were selected, and serum levels of anti-ox-LDL IgG and PAB values were measured and compared with 40 matched healthy controls. Systolic and diastolic functions were determined for all patients. RESULTS: PAB values were significantly higher in patients than in controls (p < 0.001), whilst serum anti-ox-LDL concentrations were not statistically different between the 2 groups (p = 0.821). However, after adjustment for high-density lipoprotein cholesterol, the patients had higher anti-ox-LDL levels (p = 0.04). Total PAB values were inversely associated with ejection fraction (r = -0.326, p = 0.031), but this was not the case for anti-ox-LDL in either group (p > 0.05). CONCLUSION: Serum concentrations of a marker of oxidative stress (PAB values) are inversely associated with cardiac function. PAB is a relatively simple index that could be incorporated into risk assessment in CAD patients. Anti-ox-LDL IgG antibody concentration does not appear to reflect total oxidative stress as assessed by PAB.

Anti-heat shock protein 27 titers and oxidative stress levels are elevated in patients with valvular heart disease.

We studied the immune responses to heat shock protein (Hsp)-27 and pro-oxidant-antioxidant balance (PAB) values in patients with valvular heart disease, but free of angiographically evident coronary artery disease (CAD). Patients who were candidates for valvuloplasty surgery and 30 healthy matched controls were recruited. The anti-Hsp-27 antibody titers were 0.35 ± 0.04 absorbency units (AU) in the valvuloplasty group, being significantly higher than for the controls (0.11 ± 0.02 AU; P < .05). The PAB values were significantly higher in cases (134.67 ± 13.69 Hamidi-Koliakos(HK) unit) when compared with controls (49.78 ± 6.75 HK unit; P < .05). In cases, the ejection fraction was inversely correlated with anti-Hsp-27 antibody (P < .05) but was not significantly related to PAB values (P > .05). Based on the echocardiographic findings, the patients had no evident heart failure, but the high levels of anti-Hsp-27 and PAB values in patients with valvular heart disease may indicate that these variables can be used as markers of heart failure. However, a longitudinal study is required to confirm this hypothesis.

Changes in plasma level of heat shock protein 27 after acute coronary syndrome.

We assessed the association between serum heat shock protein 27 (Hsp-27)concentrations in patients with acute coronary syndrome (ACS) and compared them with healthy participants. Patients with ACS (n = 75) were recruited and their biochemical parameters were compared with 75 healthy participants. Heat shock protein 27 concentrations were measured from blood samples taken on admission and 12 hours after the onset of chest pain. In the patient group, Hsp-27 concentrations (31.62 [20.12-38.51] ng/mL) in the first blood samples were significantly (P < .001) higher than in control samples (20.12 [16.67-28.17] ng/mL). In patients, serum Hsp-27 levels on admission were significantly (P < .001) higher than for the samples collected 12 hours after the onset of chest pain (25.87 [15.52-31.62]); the latter did not differ significantly from samples of healthy controls. In conclusion, serum Hsp-27 concentrations are elevated in the early hours following ACS, but fall to levels near to those in healthy individuals after about 12 hours from the onset of chest pain.