M1 linear ubiquitination of LKB1 inhibits vascular endothelial cell injury in atherosclerosis through activation of AMPK.

Endothelial cell injury is confirmed to be the initial step in the atherosclerosis (AS) process. Here, we tried to elucidate the role of liver kinase B1 (LKB1) and adenosine phosphate protein kinase (AMPK) in modulating vascular endothelial cells (VECs) in AS. High-fat feed (HFD)-induced AS rat models were prepared and treated with AMPK activator A-769662 alone or combined with chloroquine. An analysis of VEC injury, inflammation response, and autophagy followed it. The M1 linear ubiquitination of LKB1 was assessed by co-immunoprecipitation. The interaction between LKB1 and AMPK was analyzed. Primary aortic VECs were isolated and induced by LPS to verify the effects of LKB1 and AMPK on VEC injury in AS. Activation of AMPK reduced the VEC injury and inflammatory response of VECs and promoted autophagy caused by AS. LKB1 could regulate the activation of AMPK in AS. M1 linear ubiquitination enhanced LKB1 activity and increased AMPK activation to protect against VEC injury in AS, which was validated by in vitro experiments. Our current study highlighted that M1 linear ubiquitination of LKB1 may induce the activation of LKB1 to activate AMPK, which inhibited VEC injury in AS.

A laser platform incorporating a novel 524 nm laser pumped by a commercial hair removal laser effectively treats facial redness and lower-extremity spider veins.

BACKGROUND AND OBJECTIVES: Treatment of vascular lesions is one of the main applications of cutaneous laser technology, while the other is laser hair removal. We present here a vascular laser pumped by a commercial hair removal laser. STUDY DESIGN/MATERIALS AND METHODS: A novel 524 nm vascular laser was designed using a 755 nm hair removal laser as a pumping source. This 524 nm vascular laser was used to treat facial redness and leg telangiectasias in 24 subjects. Four treatments were administered to the face at 4-6-week intervals and final photographs were taken 8 weeks following the final treatment, while two treatments were administered to lower-extremity spider veins at 2-month intervals with follow-up photographs 3 months following the final treatment. Blinded analysis of digital images was performed by two physicians not involved in the study. RESULTS: Blinded evaluation of digital photographs revealed an average improvement score of 3.3 ± 1.7 (mean ± SEM) on a 0-10 scale for removing facial redness (p < 0.001), representing a 33% improvement. Leg veins improved an average of 51% corresponding to a score of 5.1 ± 2.0 (p < 0.001). Side effects were mild and limited to erythema, purpura, edema, and one instance of mild hyperpigmentation. CONCLUSIONS: This novel 524 nm laser is safe and effective for treating vascularity on the face and legs, and proves the ability to create a laser platform incorporating a hair removal laser which then can be used as a pumping source for the attached vascular laser module.

Downregulation of interferon-induced protein with tetratricopeptide repeats 3 relieves the inflammatory response and myocardial fibrosis of mice with myocardial infarction and improves their cardiac function.

Myocardial infarction (MI) is a common cardiovascular disease with high morbidity and mortality. In this study, we explored the role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in MI. MI was induced by ligation of the left anterior descending coronary artery. Lentivirus-mediated RNA interference of IFIT3 expression was performed by tail vein injection 72 h before MI modeling. Cardiac injury indexes and inflammatory response were examined 3 days after MI. Cardiac function indexes, infarct size, and cardiac fibrosis were assessed 4 weeks after MI. IFIT3 expression was upregulated in myocardial tissues at both 3 days and 4 weeks after MI. Knockdown of IFIT3 significantly relieved the myocardial injury, as evidenced by the decrease in serum levels of cTnI and CK-MB. In addition, IFIT3 knockdown significantly reduced the number of CD68+ macrophages and the levels of interleukin-1ß, interleukin-6, and tumor necrosis factor-α, indicating that the inflammatory response was relieved. Moreover, IFIT3 silencing also significantly improved cardiac function and reduced infarct size, myocardial fibrosis, and collagen content in mice with MI. Mechanically, the present study showed that the activation of the mitogen-activated protein kinase (MAPK) pathway was observed in myocardial tissues of MI mice, which was blocked by IFIT3 knockdown, as indicated by the decreased phosphorylation of JNK, p-38, and ERK. Collectively, our results revealed the role of IFIT3 in the inflammatory response and myocardial fibrosis after MI, indicating that IFIT3 might be a potential target for MI treatment.

Platelet-to-lymphocyte ratio relates to poor prognosis in elderly patients with acute myocardial infarction.

BACKGROUND: The platelet to lymphocyte ratio (PLR) is a novel biomarker to predict the prognosis of acute myocardial infarction (AMI) patients. AIM: The study aimed to evaluate the in-hospital outcomes of elderly patients with AMI and assessed the prognostic value of PLR on in-hospital adverse events. METHODS: A total of 1,001 patients were divided into an older group (n = 560) and a younger group (n = 441) based on age ≥ 60 years and successfully underwent primary percutaneous coronary intervention (PCI) within 12 h after presentation. Total white blood cells (WBCs), neutrophils, lymphocytes, and platelets counts were measured at admission. RESULTS: The incidence of heart rupture, acute heart failure, total adverse events, and death resulting from all events were significantly higher in patients ≥ 60 years than in younger patients, whereas the incidence of postoperative angina and reinfarction were similar between groups. Regarding blood counts, total white blood cells, neutrophils, lymphocytes, and platelets were lower in the older group than in the younger group. The platelet-to-lymphocyte ratio (PLR) was significantly higher in the older group. In receiver operating characteristic curve analysis, high PLR > 147 predicted adverse events (specificity 72% and sensitivity 63%). In multiple logistic regression analysis, age, hypertension, and PLR were identified as independent predictors of adverse events. CONCLUSIONS: The in-hospital outcomes of elderly patients with acute myocardial infarction were poor. PLR was an independent risk factor for in-hospital adverse events, which suggested that strong inflammation and prothrombotic status may contribute to the poor prognoses of elderly patients.

The First Commercial 730 nm Picosecond-Domain Laser is Safe and Effective for Treating Multicolor Tattoos.

BACKGROUND AND OBJECTIVES: Laser-pumped lasers enable driving a secondary wavelength through pumping with a primary device. Here we investigate the first 730 nm laser-pumped laser for efficacy in tattoo removal. STUDY DESIGN/MATERIALS AND METHODS: Fifteen subjects with 20 tattoos were enrolled to investigate the effect of a new 730 nm, titanium-sapphire laser-pumped laser at removing decorative tattoos. A total of four treatments were administered and photographic improvement of pre- and post-treatment cross-polarized digital images was evaluated by four blinded physician observers using an 11-point scale. RESULTS: Blinded assessment of pre- and post-treatment images found 70%, 77%, 83%, 83%, 26%, and 8% clearance from baseline images for black, green, blue, purple, red and yellow pigments, respectively. Side effects were limited to pinpoint bleeding and erythema immediately after treatment and some crusting and scale up to 1-2 weeks following treatment, and a localized allergic reaction in a single subject. There was no scarring or pigmentary alteration visible in any follow-up images. CONCLUSION: The new 730 nm, picosecond-domain, titanium-sapphire, laser-pumped laser is safe and effective for removing multicolored tattoos. Green, blue, and purple pigments cleared the most as expected, but black ink cleared more completely than was predicted. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Changes in the expression of interleukin-10 in myocardial infarction and its relationship with macrophage activation and cell apoptosis.

BACKGROUND: Currently, the role of interleukin-10 (IL-10) as an anti-inflammatory factor in the occurrence and development of heart disease is still unclear. This study aimed to observe the dynamic changes in the expression of IL-10 in serum and myocardial tissues and to investigate the relationship of IL-10 expression with macrophage activation and cardiomyocyte apoptosis during the occurrence of myocardial infarction (MI). METHODS: Mice models with MI were prepared by ligating the anterior descending branch of the coronary artery. The animals were classified into the sham operation group (the control group), and the day 1, 7, 14, and 28 MI groups based. RESULTS: On days 7 and 14, the cells with positive IL-10 expression were largely distributed in the infarct areas, while cells with positive IL-10 expression were decreased on day 28. Serum IL-10 was significantly positively correlated with IL-10 protein expression in myocardial tissues. Moreover, Bcl-2 and Bax protein expression in myocardial tissues, along with the ratio of Bcl-2/Bax proteins, were gradually elevated with prolonged time of infarction. The expression of arginase protein increased gradually too. There were positive correlations between IL-10 and arginase expressions, and between the expressions of Bcl-2 and Bax proteins. CONCLUSIONS: After the occurrence of MI, the expression of IL-10 first increased and then decreased in serum and myocardial tissues, with this likely affecting macrophage activation, phenotypic transformation, and the occurrence of cardiomyocyte apoptosis.

lncRNA 430945 promotes the proliferation and migration of vascular smooth muscle cells via the ROR2/RhoA signaling pathway in atherosclerosis.

The proliferation and migration of vascular smooth muscle cells (VSMCs) are major cellular events in hypertension­induced vascular remodeling, which is closely involved in the progression of atherosclerosis (AS). Although long non­coding RNAs (lncRNAs) are gaining recognition as novel regulators of VSMCs, their functioning and role in AS remain to be elucidated. In the present study, the role of lncRNA ENST00000430945 (lncRNA 430945) in AS was investigated. VSMCs transfected with a small interfering RNA (siRNA; si­430945) and a negative control (si­NC) were used. Cell Counting Kit­8, wound­healing and Transwell migration arrays were performed to determine whether lncRNA 430945 influenced VSMC proliferation and migration. Furthermore, the study examined whether a correlation exists between lncRNA 430945 and the receptor tyrosine kinase­like orphan receptor 2 (ROR2) signaling pathway. It was found that the expression of lncRNA 430945 was high in human AS tissues, which in turn promoted angiotensin II (AngII)­induced VSMC proliferation. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analyses showed that lncRNA 430945 mediated the AngII­induced upregulation of ROR2. In addition, the microarray and RT­qPCR results showed that the expression of lncRNA 430945 was increased considerably in AS tissues. The downregulation of lncRNA 430945 significantly suppressed AngII­induced VSMC proliferation and migration. In addition, ROR2 levels in VSMCs transfected with si­430945 were markedly lower than those cells transfected with si­NC. Additionally, western blotting showed that lncRNA 430945 activated the signaling pathways associated with ROR2 and Ras homolog gene family member A (RhoA). The upregulation of lncRNA 430945 in AS promoted the proliferation and migration of VSMCs via activation of the ROR2/RhoA signaling pathway. Therefore, targeting ROR2 or RhoA may be a promising technique in developing therapeutic strategies for treating AS.

Hyperuricemia is associated with short-term outcomes in elderly patients with acute myocardial infarction.

BACKGROUND: Although a lot of studies have  shown serum uric acid (SUA) could be a marker of adverse prognosis in patients with acute myocardial infarction, the role of SUA as a risk factor for myocardial infarction is controversial. This study aimed to evaluate the association between hyperuricemia and short-term outcomes of elderly patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Six hundred and seventy-three elderly patients (≥ 60 years) were divided into high-SUA-level group (group H: N = 168) and low-SUA-level group (group L: N = 505) according to the SUA levels on admission. The following primary end points were evaluated within 30 days of AMI. The adverse events included postoperative angina pectoris, heart failure (Killip class ≥ II), and death. The comparisons were made between two groups in clinical and angiographic characteristics. RESULTS: The incidences of postoperative angina pectoris, heart failure, and the total adverse cardiovascular events were significantly higher in group H than in group L. But the incidence of death was similar between groups. In group H, heart rate (HR), systolic and diastolic blood pressure, SUA, homocysteine (HCY), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and creatine kinase myocardial band (CKMB) peak were clearly higher compared with those in group L. The results of logistic regression showed that the incidence of 30-day adverse events was closely related to TG, HCY and SUA. CONCLUSIONS: An elevated SUA level may be related to the short-term outcomes and seems to be an independent predictor of 30-day cardiovascular events in elderly patients with STEMI.

Mid-infrared Lasers for Medical Applications: introduction to the feature issue.

This feature issue contains a series of papers that report the most recent advances in the field of mid-infrared light sources used for medical applications, including tissue imaging, reconstruction, excision, and ablation. Many biomolecular compounds have strong resonances in the mid-infrared region and medicine is ideally suited to exploit this. The precision, sterility, and versatility of light in mid-infrared is opening more opportunities and this feature issue captures some of the most exciting.

miR-3646 promotes vascular inflammation and augments vascular smooth muscle cell proliferation and migration in progression of coronary artery disease by directly targeting RHOH.

Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide and the number of individuals at CAD risk is increasing. To better manage cardiovascular disease, improved tools for risk prediction including the identification of novel accurate biomarkers are needed. MicroRNAs (miRNAs) are small non-coding RNAs that modulate the expression of protein-coding genes at the post-transcription level and their dysregulated expression has been implicated in various pathogenic processes including cardiovascular disease. Circulating miRNAs have been widely recommended as potential biomarkers for many diseases including coronary artery disease. In the present study, we found that miR-3646 was significantly upregulated in the serum samples of CAD patients and in the mice with acute myocardial infarction (AMI) compared with the healthy control group via using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Moreover, the serum levels of miR-3646 were significantly positively correlated with the expression of IL-6 both in CAD patient samples and AMI mice samples. In human THP-1 macrophages, transfection with miR-3646 mimic elevated the expression of IL-6 while silence of miR-3646 suppressed the IL-6 level. Further exploration of the downstream targets of miR-3646 identified that blocking RHOH expression also could upregulate IL-6 expression. In addition, our findings also showed that miR-3646 promoted vascular smooth muscle cell (VSMC) proliferation and migration by targeting RHOH. These results demonstrate that the miR-3646-RHOH axis may serve as a key regulator in the progression of CAD by modulating vascular inflammation and regulating the biologic behaviors of VSMCs.

Predictive Nomogram of RAGE Genetic Polymorphisms and Metabolic Risk Factors for Myocardial Infarction Risk in a Han Chinese Population.

We investigated the association of 4 well-characterized polymorphisms in receptor for the advanced glycation end-product ( RAGE) gene with myocardial infarction (MI) risk and the changes in metabolic risk factors among 717/612 patients/controls, with the aim of constructing a predictive nomogram. The genotype/allele distributions differed significantly between the 2 groups for T-429C ( Pgenotype/allele = .004/.001) and G1704T ( P < .001/.001). T-429C was significantly associated with MI risk, especially under a recessive model (adjusted odds ratio: 2.24, 95% confidence interval: 1.33-3.79, P = .003). For G1704T, significance was detected under additive (1.37; 1.12-1.67; P = .002) and recessive (3.86; 2.27-6.57; P < .001) models. There were significant differences in blood pressure and low-density lipoprotein cholesterol (LDL-C) across T-429C genotypes and in total cholesterol and LDL-C across G1704T genotypes. The overall best multifactor dimensionality reduction model included dyslipidemia, G1704T, and T-429C. Further predictive nomogram on 2 significant polymorphisms, blood pressure and lipids, showed a better predictive capability (concordance index = 0.716, P < .001). Altogether, we identified 2 polymorphisms of RAGE, T-429C and G1704T, which interacted with metabolic risk factors associated with the occurrence of MI. We also constructed a genetic-metabolic nomogram that can better predict MI risk.

The association of eight potentially functional polymorphisms in five adrenergic receptor-encoding genes with myocardial infarction risk in Han Chinese.

Adrenergic receptors play a key role in activating the sympathetic nervous system, which often accompanies with the development of myocardial infarction (MI). Here, we aimed to test the association of eight potentially functional polymorphisms in five adrenergic receptor-encoding genes with MI risk. Genotypes were available for 717 MI patients and 612 controls. There were no detectable deviations from the Hardy-Weinberg equilibrium for all study polymorphisms. Allele frequencies differed remarkably for ADRA2B D/I (P<0.001), ADRB1 Ser49Gly (P=0.002), ADRB2 Gln27Glu (P=0.005), and ADRB3 Trp64Arg (P<0.001) polymorphisms, even after the Bonferroni correction. Systolic blood pressure was significantly lower in ADRA2B II genotype carriers than in the DD genotype carriers (P=0.006), while plasma high-density lipoprotein cholesterol was significantly higher in patients carrying ADRA2B I allele and ADRB1 49Ser allele than in patients with the DD genotype and 49Gly/49Gly genotype, respectively (P=0.018 and 0.033). Overall best interaction model consisted of ADRA2B D/I, ADRB1 Ser49Gly, dyslipidemia and hypertension, with the highest testing accuracy of 0.627 and the maximal 10-fold cross-validation consistency (P=0.017). Finally, a nomogram was depicted based on four significant polymorphisms and metabolic risk factors, and it had a better predictive utility and was internally validated with a discrimination C-index of 0.723 (P<0.001). Altogether, we identified two polymorphisms, ADRA2B D/I and ADRB1 Ser49Arg, which not only altered genetic susceptibility to MI, but also impacted on blood pressure and plasma lipid changes, and their combination with metabolic risk factors constituted the overall best interaction model.

The Effects of Carvedilol on Cardiac Function and the AKT/XIAP Signaling Pathway in Diabetic Cardiomyopathy Rats.

OBJECTIVES: Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction, myocardial inflammation, interstitial fibrosis and cardiomyocytes apoptosis. The present study aimed to investigate the effects of carvedilol on cardiac function and the AKT/XIAP signaling pathway in DCM rats. METHODS: Male Wistar rats were randomly divided into 3 groups: the control group, diabetic mellitus (DM) group and DM with carvedilol treatment group. DM rats were induced by streptozotocin accompanied by high energy intake. Carvedilol was orally administered at a dose of 10 mg/kg/day. After 16 weeks, the interrelated blood data were detected by biochemical analysis. Cardiac function was evaluated by echocardiography and the serum NT-proBNP level. The changes of myocardium ultrastructural and fibrosis were determined by electron microscopy and Masson's staining. Apoptotic cells were examined by TUNEL staining and interrelated proteins were measured by immunohistochemical and Western blots. RESULTS: Rats in the DM group showed significant serum elevation of glucose, cholesterol, triglyceride, NT-proBNP, IL-1ß and TNF-α, along with decreased cardiac function. Moreover, in the DM group, the levels of myocardial apoptosis and fibrosis were all increased accompanied by upregulation of caspase-3 and downregulation of phos-AKT and phos-XIAP, whereas carvedilol treatment prevented or reversed all the changes without influencing plasma levels of glucose, cholesterol and triglyceride. CONCLUSIONS: The AKT/XIAP signaling pathway may be involved in DCM. Carvedilol can improve cardiac function, possibly not only by upregulating the AKT/XIAP antiapoptotic signaling pathway and subsequently attenuating myocardial fibrosis, but also through suppressing the myocardial inflammation response.

Screening and identification of microRNA involved in unstable angina using gene-chip analysis.

Increasing evidence has suggested that microRNA (miRNA) may play a role in the pathogenesis of cardiovascular disease, which has led to a greater understanding of the complex pathophysiological processes underlying unstable angina (UA). The present study aimed to investigate changes in the miRNA expression profiles of patients with UA using gene-chip analysis, in order to further elucidate the pathogenesis of UA. Total RNA was extracted and purified from plasma samples collected from patients with UA and healthy controls. The samples underwent microarray analysis using an Exiqon miRCURY LNA™ microRNA Array. Differentially expressed miRNAs were identified by volcano plot filtering, and were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, functional annotation of the differentially expressed miRNAs involved gene ontology analyses. Among the 212 miRNAs differentially expressed between the two groups, 82 were upregulated and 130 were downregulated. Notably, the results of the RT-qPCR were consistent with the gene-chip results. The miRNAs identified in the present study may be potential novel biomarkers for the prevention and early diagnosis of UA. Furthermore, the results of the present study suggested that UA occurs as a result of complex and dynamic processes regulated by numerous factors, including multiple miRNAs.

Multiple characteristics analysis of Alzheimer's electroencephalogram by power spectral density and Lempel-Ziv complexity.

To investigate the electroencephalograph (EEG) background activity in patients with Alzheimer's disease (AD), power spectrum density (PSD) and Lempel-Ziv (LZ) complexity analysis are proposed to extract multiple effective features of EEG signals from AD patients and further applied to distinguish AD patients from the normal controls. Spectral analysis based on autoregressive Burg method is first used to quantify the power distribution of EEG series in the frequency domain. Compared with the control group, the relative PSD of AD group is significantly higher in the theta frequency band while lower in the alpha frequency bands. In order to explore the nonlinear information, Lempel-Ziv complexity (LZC) and multi-scale LZC is further applied to all electrodes for the four frequency bands. Analysis results demonstrate that the group difference is significant in the alpha frequency band by LZC and multi-scale LZC analysis. However, the group difference of multi-scale LZC is much more remarkable, manifesting as more channels undergo notable changes, particularly in electrodes O1 and O2 in the occipital area. Moreover, the multi-scale LZC value provided a better classification between the two groups with an accuracy of 85.7 %. In addition, we combine both features of the relative PSD and multi-scale LZC to discriminate AD patients from the normal controls by applying a support vector machine model in the alpha frequency band. It is indicated that the two groups can be clearly classified by the combined feature. Importantly, the accuracy of the classification is higher than that of any one feature, reaching 91.4 %. The obtained results show that analysis of PSD and multi-scale LZC can be taken as a potential comprehensive measure to distinguish AD patients from the normal controls, which may benefit our understanding of the disease.

MicroRNA 28-5p regulates ATP-binding cassette transporter A1 via inhibiting extracellular signal-regulated kinase 2.

The biological function of the intronic microRNA-28 (miR-28) may be associated with the biological roles of its host gene, LIM domain lipoma­preferred partner (LPP). LPP has been reported to promote smooth muscle cell migration in arterial injury and atherosclerosis. However, the mechanism of miR­28 in atherosclerosis remains unclear. In the current study, the aim was to validate the inhibitory effect of miR­28­5p on extracellular signal­regulated kinase 2 (ERK2), to investigate its biological role in atherosclerosis and its association with cardiovascular disease. Western blotting and stem­loop reverse transcription­quantitative polymerase chain reaction combined with TaqMAN microRNA analysis was conducted. The current study demonstrated that miR­28­5p upregulated the expression of ATP­binding cassette transporter A1 (ABCA1) via the inhibition of ERK2 in HepG2 cells. In addition, increased levels of plasma miR­28­5p were positively correlated with the levels of high­density lipoprotein cholesterol in patients with unstable angina. This suggests that miR-28-5p participates in atherosclerosis via ERK2-mediated upregulation of the ABCA1 pathway.

Correlation Between Hyperhomocysteinemia and Outcomes of Patients With Acute Myocardial Infarction.

Overwhelming clinical and epidemiological studies have identified elevated plasma total homocysteine (Hcy) as new important risk factor for atherosclerotic vascular disease. But the relationship between outcome and hyperhomocysteinemia in patients with acute myocardial infarction (AMI) has been rarely reported. This study aimed to evaluate the association between hyperhomocysteinemia and short-term outcomes of patients with AMI. Eight hundred five patients were divided into high Hcy level group (group H: N = 457) and low Hcy level group (group L: N = 348) according to the plasma Hcy levels of 15 mmol/L. The comparisons were made between 2 groups in the following aspects: sex, hypertension, diabetes, hyperlipidemia, the time for symptom from onset to percutaneous coronary intervention, homoccyteine, creatine phosphokinase isoenzyme (creatine kinase myocardial band), and the incidence of 30-day adverse events. The incidences of heart failure, cardiac rupture, death, and the total adverse cardiovascular events were statistically significantly higher in group H than in group L. But the incidence of postoperative angina pectoris and reinfarction was similar between groups. The results of logistic regression showed that the incidence of 30-day adverse events was closely related to the age and the level of Hcy. An elevated plasma total Hcy level in patients with AMI experienced pemutaneous coronary intervention may be related to the short-term outcomes. An elevated high plasma Hcy level also seems to be an independent predictor of 30-day cardiovascular events in patients with AMI.

Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.

Although statins are generally well-tolerated drugs, recent cases of drug-induced liver injury associated with their use have been reported. A 52-year-old Chinese man reported with liver damage, which appeared 12 hours after beginning treatment with fluvastatin. Patient presented with complaints of increasing nausea, anorexia, and upper abdominal pain. His laboratory values showed elevated creatine kinase and transaminases. Testing for autoantibodies was also negative. The liver biochemistries eventually normalized within 3 weeks of stopping the fluvastatin. Therefore, when prescribing statins, the possibility of hepatic damage should be taken into account.