Association between thyroid dysfunction and dysglycaemia: a prospective cohort study.

AIMS: To compare the incidence of hyperglycaemia among participants with low, elevated and normal serum thyroid-stimulating hormone concentration, as well as the incidence of abnormal thyroid function test results among participants with normal blood glucose and those with hyperglycaemia. METHODS: In a prospective study, a cohort of 72 003 participants with normal, low and elevated serum thyroid-stimulating hormone concentration were followed from the study beginning to the first report of diabetes and prediabetes. A proportional hazards regression model was used to calculate the hazard ratios and 95% CIs for each outcome, adjusting for age, sex, education level, smoking, alcohol consumption and obesity. Analyses for the association between dysglycaemia and incident abnormal thyroid function test were also conducted. RESULTS: During a median 2.6 year follow-up, the incident rates for dysglycaemia, particularly prediabetes, were substantially higher in participants with elevated thyroid-stimulating hormone concentrations at baseline, while the rates for participants with normal and low thyroid-stimulating hormone were similar. After controlling for risk factors, participants with elevated thyroid-stimulating hormone retained a 15% increase in risk of prediabetes (adjusted hazard ratio 1.15, 95% CI 1.04-1.26), but were not at greater risk of diabetes (adjusted hazard ratio 0.96, 95% CI 0.64-1.44). By contrast, participants with normal and low thyroid-stimulating hormone concentrations had similar dysglycaemia risks. Participants with diabetes and prediabetes were not at greater risks of developing abnormal thyroid function test results when compared with participants with euglycaemia. CONCLUSIONS: People with elevated serum thyroid-stimulating hormone concentration are at greater risk of developing prediabetes. Whether this includes a greater risk of developing frank diabetes may require an extended period of follow-up to clarify.

Kidney-targeting Smad7 gene transfer inhibits renal TGF-ß/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways, and improves diabetic nephropathy in mice.

AIMS/HYPOTHESIS: The TGF-ß/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways have been shown to play a critical role in the development of renal fibrosis and inflammation in diabetic nephropathy. We therefore examined whether targeting these pathways by a kidney-targeting Smad7 gene transfer has therapeutic effects on renal lesions in the db/db mouse model of type 2 diabetes. METHODS: We delivered Smad7 plasmids into the kidney of db/db mice using kidney-targeting, ultrasound-mediated, microbubble-inducible gene transfer. The histopathology, ultrastructural pathology and pathways of TGF-ß/SMAD2/3-mediated fibrosis and NF-κB-dependent inflammation were evaluated. RESULTS: In this mouse model of type 2 diabetes, Smad7 gene therapy significantly inhibited diabetic kidney injury, compared with mice treated with empty vectors. Symptoms inhibited included: (1) proteinuria and renal function impairment; (2) renal fibrosis such as glomerular sclerosis, tubulo-interstitial collagen matrix abundance and renal inflammation, including Inos (also known as Nos2), Il1b and Mcp1 (also known as Ccl2) upregulation, as well as macrophage infiltration; and (3) podocyte and endothelial cell injury as demonstrated by immunohistochemistry and/or electron microscopy. Further study demonstrated that the improvement of type 2 diabetic kidney injury by overexpression of Smad7 was associated with significantly inhibited local activation of the TGF-ß/SMAD and NF-κB signalling pathways in the kidney. CONCLUSIONS/INTERPRETATION: Our results clearly demonstrate that kidney-targeting Smad7 gene transfer may be an effective therapy for type 2 diabetic nephropathy, acting via simultaneous modulation of the TGF-ß/SMAD and NF-κB signalling pathways.

Social Well-Being, Psychological Factors, and Chronic Conditions Among Older Adults.

Background: Aging is characterized by the decline in physical health, functional status, and loss of social roles and relationships that can challenge the quality of life. Social well-being may help explain how aging individuals experience declining physical health and social relationships. Despite the high prevalence of chronic conditions among older adults, research exploring the relationship between social well-being and chronic disease is sparse. Objectives: The study aims were to investigate the relationship between social well-being and psychological factors (e.g., perceived control, life satisfaction, self-esteem, active coping, optimism, and religious coping) by chronic condition in older adults. Design: Cross-sectional study. Participants: The current study comprises older adults (N = 1,251, aged ≥ 65 y) who participated in the third wave of the National Survey of Midlife in the United States (i.e., MIDUS). Setting: MIDUS was conducted on a random-digit-dial sample of community-dwelling, English-speaking adults. Measurements: Six instruments representing psychological resources (life satisfaction, perceived control, self-esteem, optimism, active coping, and religious coping) and five dimensions of social well-being (social actualization, social coherence, social acceptance, social contribution, social integration) were measured. An index of chronic disease comprised of self-reported data whether they had received a physician's diagnosis for any chronic conditions over the past year. Results: The findings indicated that the individuals without chronic conditions had significantly higher social integration, social acceptance, and social contribution scores than the individuals with chronic conditions (t = 2.26, p < 0.05, t = 2.85, p < 0.01, and t = 2.23, p < 0.05, respectively). For individuals diagnosed with more than one chronic condition, perceived control, self-esteem, and optimism were positively related to their social well-being (ß = .33, p < .001, ß = .17, p < .001, and ß = .33, p < .001, respectively). Conclusion: Findings suggested that older adults with multiple chronic conditions have a decrease in social well-being. Chronic disease management programs may help increase social well-being among individuals with multiple chronic conditions.

Comparison of clinical outcomes of edoxaban versus apixaban, dabigatran, rivaroxaban, and vitamin K antagonists in patients with atrial fibrillation in Germany: A real-world cohort study.

BACKGROUND: The aim of the study was to compare the real-world effectiveness and safety in atrial fibrillation (AF) patients treated with edoxaban versus other oral anticoagulants (OACs) (apixaban, dabigatran, rivaroxaban, and vitamin K antagonists [VKA]) in Germany. METHODS AND RESULTS: Using a representative database of 3.5 million statutory health-insured lives in Germany, a retrospective cohort study was conducted to examine ischemic stroke (IS) or systemic embolism (SE) and major bleeding in AF patients initiating anticoagulant therapy from January 2014 through June 2017. Inverse probability of treatment weighting using propensity score was applied for baseline covariate adjustment. Cox proportional hazards models were used to estimate the adjusted risk (hazard ratio [HR]) of each outcome comparing edoxaban versus other OACs. Among 21,038 patients treated with OACs, 1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA patients were included. The adjusted combined risks of IS or SE were lower (p < 0.05) for each edoxaban pairwise comparison with other OACs (HR: 0.83 vs. apixaban, 0.60 vs. dabigatran, 0.72 vs. rivaroxaban, 0.64 vs. VKA). Edoxaban favored lower risks of major bleeding compared with rivaroxaban (HR: 0.74) and VKA (HR: 0.47). No differences in the risk of major bleeding were found between edoxaban and apixaban (p = 0.33), and between edoxaban and dabigatran (p = 0.06). CONCLUSIONS: Edoxaban was associated with better effectiveness compared with other OACs in AF patients from Germany. Edoxaban also demonstrated a favorable safety profile.

Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes.

BACKGROUND: Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. METHODS: Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1µM), propofol (1µM), or propofol plus doxorubicin (given 1h post propofol). After 24h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. RESULTS: Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-δ was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. CONCLUSIONS: Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.

Effect of combining dexmedetomidine and morphine for intravenous patient-controlled analgesia.

BACKGROUND: Perioperative use of dexmedetomidine is associated with reduction in postoperative analgesic requirements. This study examined whether dexmedetomidine added to i.v. patient-controlled analgesia (PCA) morphine could improve analgesia while reducing opioid-related side-effects. METHODS: In this double-blinded, randomized, controlled study, 100 women undergoing abdominal total hysterectomy were allocated to receive either morphine 1 mg ml(-1) alone (Group M) or morphine 1 mg ml(-1) plus dexmedetomidine 5 microg ml(-1) (Group D) for postoperative i.v. PCA, which was programmed to deliver 1 ml per demand with a 5 min lockout interval and no background infusion. Cumulative PCA requirements, pain intensities, cardiovascular and respiratory variables, and PCA-related adverse events were recorded for 24 h after operation. RESULTS: Compared with Group M, patients in Group D required 29% less morphine during the 0-24 h postoperative period and reported significantly lower pain levels from the second postoperative hour onwards and throughout the study. Whereas levels of sedation were similar between the groups at each observational time point, decreases in heart rate and mean blood pressure from presurgery baseline at 1, 2, and 4 h after operation were significantly greater in Group D (by a range of 5-7 beats min(-1) and 10-13%, respectively). The 4-24 h incidence of nausea was significantly lower in Group D (34% vs 56.3%, P<0.05). There was no bradycardia, hypotension, oversedation, or respiratory depression. CONCLUSIONS: The addition of dexmedetomidine to i.v. PCA morphine resulted in superior analgesia, significant morphine sparing, less morphine-induced nausea, and was devoid of additional sedation and untoward haemodynamic changes.

Risk of Myocardial Infarction and Ischemic Stroke after Dental Treatments.

The association between invasive dental treatments (IDTs) and a short-term risk of myocardial infarction (MI) and ischemic stroke (IS) remains controversial. Bacterial dissemination from the oral cavity and systemic inflammation linked to IDT can induce a state of acute vascular dysfunction. The aim of study is to investigate the relation of IDTs to MI and IS by using case-only study designs to analyze data from a large Taiwanese cohort. A nationwide population-based study was undertaken by using the case-crossover and self-controlled case series design to analyze the Taiwanese National Health Care Claim database. Conditional logistic regression model and conditional Poisson regression model were used to estimate the risks of MI/IS. In addition, we used burn patients as negative controls to explore the potential effect of residual confounding. In total, 123,819 MI patients and 327,179 IS patients in the case-crossover design and 117,655 MI patients and 298,757 IS patients were included in the self-controlled case series design. Results from both study designs showed that the risk of MI within the first 24 wk after IDT was not significantly different from or close to unity except for a modest risk during the first week for patients without other comorbidities (odds ratios [95% confidence intervals] of 1.31 [1.08-1.58] and 1.15 [1.01-1.31] for 3 d and 7 d, respectively). We also observed no association between IDTs and IS, or the risk ratio was close to unity. IDTs did not appear to be associated with a transient risk of MI and IS in the Taiwanese population, with consistent findings from both case-only study designs. However, we cannot exclude that dental infections and diseases may yield a long-term risk of MI and IS.

Combination of opioid agonist and agonist-antagonist: patient-controlled analgesia requirement and adverse events among different-ratio morphine and nalbuphine admixtures for postoperative pain.

BACKGROUND: Nalbuphine, a mixed agonist-antagonist opioid, has a potential to attenuate the mu-opioid effects and to enhance the kappa-opioid effects. However, when morphine and nalbuphine are mixed together, the clinical interactions in different combining ratios on analgesic effect and adverse events are unknown. METHODS: This randomized, double-blind controlled study investigated five different combining ratios of morphine and nalbuphine in 311 patients undergoing gynaecologic operations. The concentrations [morphine (mg ml(-1))]/[nalbuphine (mg ml(-1))] were 1/0 in Group 1, 0.75/0.25 (ratio 1:3) in Group 2, 0.5/0.5 (ratio 1:1) in Group 3, 0.25/0.75 (ratio 3:1) in Group 4, and 0/1 in Group 5. Patient-controlled analgesia (PCA) requirement, postoperative pain, and adverse events were evaluated throughout the postoperative 24 h period. RESULTS: Twenty-four hour PCA requirements were similar among the five groups. Verbal rating scores for pain were statistically higher in Groups 2 and 4 than in Group 3. The incidences of pruritus were higher in Group 1 (15.6%) than in Group 2 (6.2%), Group 3 (3.4%), Group 4 (1.6%), and Group 5 (0%). The incidences and severity of dizziness, nausea, and vomiting were not significantly different. CONCLUSIONS: The interaction between morphine and nalbuphine in PCA admixture on analgesia is additive. Combinations of morphine and nalbuphine in PCA can decrease the incidence of pruritus, and the antipruritus effect is ratio-dependent. This may provide a novel combination strategy of opioid agonist and agonist-antagonist for postoperative pain management after gynaecologic surgery.

Phaeochromocytoma crisis--a rare indication for extracorporeal membrane oxygenation.

We report on a case of phaeochromocytoma whose initial presentation mimicked an acute myocardial infarction. Veno-arterial extracorporeal membrane oxygenation was used for the management of refractory cardiogenic shock and massive lung oedema. Suspicion and diagnosis of a phaeochromocytoma were made due to its unique clinical presentation during extracorporeal membrane oxygenation. Stabilisation of the crisis and recovery of cardiopulmonary function were achieved using the support of extracorporeal membrane oxygenation. This case highlights the difficulty in the differential diagnosis of cardiogenic shock secondary to phaeochromocytoma and the important role of extracorporeal membrane oxygenation can have in the successful resuscitation and management of these patients.

Characterization of a mammalian homolog of the Escherichia coli MutY mismatch repair protein.

A protein homologous to the Escherichia coli MutY protein, referred to as MYH, has been identified in nuclear extracts of calf thymus and human HeLa cells. Western blot (immunoblot) analysis using polyclonal antibodies to the E. coli MutY protein detected a protein of 65 kDa in both extracts. Partial purification of MYH from calf thymus cells revealed a 65-kDa protein as well as a functional but apparently degraded form of 36 kDa, as determined by glycerol gradient centrifugation and immunoblotting with anti-MutY antibodies. Calf MYH is a DNA glycosylase that specifically removes mispaired adenines from A/G, A/7,8-dihydro-8-oxodeoxyguanine (8-oxoG or GO), and A/C mismatches (mismatches indicated by slashes). A nicking activity that is either associated with or copurified with MYH was also detected. Nicking was observed at the first phosphodiester bond 3' to the apurinic or apyrimidinic (AP) site generated by the glycosylase activity. The nicking activity on A/C mismatches was 30-fold lower and the activity on A/GO mismatches was twofold lower than that on A/G mismatches. No nicking activity was detected on substrates containing other selected mismatches or homoduplexes. Nicking activity on DNA containing A/G mismatches was inhibited in the presence of anti-MutY antibodies or upon treatment with potassium ferricyanide, which oxidizes iron-sulfur clusters. Gel shift analysis showed specific binding complex formation with A/G and A/GO substrates, but not with A/A, C.GO, and C.G substrates. Binding is sevenfold greater on A/GO substrates than on A/G substrates. The eukaryotic MYH may be involved in the major repair of both replication errors and oxidative damage to DNA, the same functions as those of the E. coli MutY protein.

Elevation of transforming growth factor alpha and its relationship to the epidermal growth factor and alpha-fetoprotein levels in patients with hepatocellular carcinoma.

A radioimmunoassay for transforming growth factor alpha (TGF-alpha) using synthetic rat sarcoma transforming growth factor and its rabbit polyclonal antibody has been developed. Using radioimmunoassays, the urinary TGF-alpha and epidermal growth factor (EGF) concentrations in 31 patients with hepatocellular carcinoma (HCC), 15 probable HCC, four metastatic liver cancer, and 33 age, sex-matched healthy controls were determined. For the first time, we have shown that the average TGF-alpha concentration for HCC patients was 21.5 +/- 20.3 micrograms per g creatinine, significantly higher than that of healthy subjects, 4.9 +/- 2.8 micrograms per g creatinine (P less than 0.001). There was no statistical difference in the level of EGF between HCC patients and controls (40.9 +/- 29.3 versus 46.2 +/- 16.6 micrograms per g creatinine; P greater than 0.05). The ratio of EGF/TGF-alpha between HCC patients (3.37 +/- 4.42) and controls (15.5 +/- 13.0) was significantly different (P less than 0.001). Among patients, 65% (20 of 31) of HCC cases and 87% (13 of 15) of probable HCC cases showed a marked elevation of TGF-alpha levels. We found only 16% (five of 31) of HCC cases with increased EGF level. EGF excretion was inversely age related. Serum total protein concentration and alkaline phosphatase activity were positively correlated to EGF concentration (r = 0.522, P less than 0.01 and rt = 0.393, P less than 0.05, respectively). There was no correlation between biochemical functions of liver and TGF-alpha concentration in HCC patients. Our results also suggested that TGF-alpha may be a useful complementary tumor marker for management of patients with clinical manifestation of HCC who have low alpha-fetoprotein levels.

Clinical Factors Implicated in Primary Graft Dysfunction After Heart Transplantation: A Single-center Experience.

BACKGROUND: Primary graft dysfunction (PGD) is a frequent complication after cardiac transplantation and remains one of the leading causes of mortality in these patients. The objective of this case-control study is to identify donor and surgical procedure's factors associated with PGD, and further guide possible strategies to prevent PGD. METHODS: Retrospective analysis of the medical records of patients who underwent cardiac transplantation at Memorial Hermann Hospital at Texas Medical Center between October 2012 and February 2015. RESULTS: The study population included 99 patients, of which 18 developed PGD. Univariate analysis of donor characteristics revealed opioid use (P = .049) and death owing to anoxia (P = .021) were associated with PGD. The recipient/donor blood type match AB/A was significantly associated with PGD (P = .031). Time from brain death to aortic cross clamp (TBDACC) of ≥3 and ≥5 days were also found to be associated with PGD (P = .0011 and .0003, respectively). Multivariate analysis confirmed that patients with a time from brain death to aortic cross clamp ≥3 and ≥5 days had lesser odds of developing PGD (odds ratio, 0.098 [P = .0026] and OR, 0.092 [P = .0017], respectively]. CONCLUSIONS: Our study showed that a longer time from brain death to aortic cross clamp was associated with lower odds of developing PGD. Therefore, postponing heart procurement for a few days after brain death seems to be beneficial in preventing PGD.

Visualizing chemical states and defects induced magnetism of graphene oxide by spatially-resolved-X-ray microscopy and spectroscopy.

This investigation studies the various magnetic behaviors of graphene oxide (GO) and reduced graphene oxides (rGOs) and elucidates the relationship between the chemical states that involve defects therein and their magnetic behaviors in GO sheets. Magnetic hysteresis loop reveals that the GO is ferromagnetic whereas photo-thermal moderately reduced graphene oxide (M-rGO) and heavily reduced graphene oxide (H-rGO) gradually become paramagnetic behavior at room temperature. Scanning transmission X-ray microscopy and corresponding X-ray absorption near-edge structure spectroscopy were utilized to investigate thoroughly the variation of the C 2p(π*) states that are bound with oxygen-containing and hydroxyl groups, as well as the C 2p(σ*)-derived states in flat and wrinkle regions to clarify the relationship between the spatially-resolved chemical states and the magnetism of GO, M-rGO and H-rGO. The results of X-ray magnetic circular dichroism further support the finding that C 2p(σ*)-derived states are the main origin of the magnetism of GO. Based on experimental results and first-principles calculations, the variation in magnetic behavior from GO to M-rGO and to H-rGO is interpreted, and the origin of ferromagnetism is identified as the C 2p(σ*)-derived states that involve defects/vacancies rather than the C 2p(π*) states that are bound with oxygen-containing and hydroxyl groups on GO sheets.

Circadian stage-dependent effects of epidermal growth factor on deoxyribonucleic acid synthesis in ten different organs of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular gland of mice was injected ip at different circadian stages into separate subgroups of adult male CD2F1 mice. Subsequent to each of the five time points of injection (0900, 1500, 1800, 2100, and 0300 h for animals standardized to 12 h of light alternating with 12 h of darkness: light, 0600-1800 h; dark, 1800-0600 h), five animals were killed at 4, 8, and 12 h after the EGF injection; comparable control groups were injected only with the carrier substance. Thirty minutes before sacrifice, each mouse was injected ip with 24 muCi [3H]thymidine. Incorporation of [3H]thymidine into the DNA of the aorta, lung, liver, cornea, testes, kidney, parotid, thymus, spleen, and bone marrow as well as the mitotic index of the corneal epithelium was determined. The results indicate that EGF may play a role in the positive control of growth of many of these tissues, especially the aorta, lung, liver, and cornea. EGF may also play a role in inhibiting growth of the thymus, spleen, and bone marrow. Moreover, the stimulatory effect of EGF on the growth of the various tissues appears to be especially enhanced in mice injected at 1500 h and killed 4 h later at 1900 h.

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the duodenum, jejunum, ileum, caecum, colon, and rectum of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular salivary glands of mice was injected ip at five different circadian phases into separate sub-groups of adult male CD2F1 mice that had been standardized to 12 h of light alternating with 12 h of darkness. Comparable control groups were injected only with the carrier substance. Four, 8, and 12 h after each of the five injection times, subgroups of five mice were killed. Thirty minutes before sacrifice, each mouse was injected ip with 24 mu Ci tritiated thymidine ([3H]-TdR). Incorporation of [3H]TdR into the DNA of the duodenum, jejunum, ileum, cecum, colon, and rectum was determined. The results demonstrate for the first time that EGF has a stimulatory effect on DNA synthesis in these tissues, particularly in the colon and rectum. Under the conditions of this study, the stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were more dramatic than those in the three regions of the small intestine; in fact, DNA synthesis in the latter was occasionally statistically significantly decreased, particularly for mice killed during the dark phase. Stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were noticed as early as 4 h after injection; however, maximal stimulation occurred 8 and 12 h post injection.

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the tongue, esophagus, and stomach of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular gland of mice was injected ip at different circadian phases into separate subgroups of adult male CD2F1 mice. Subsequent to each of the five time points of injection (0900, 1500, 1800, 2100, and 0300 h for animals standardized to 12 h of light alternating with 12 h of darkness), five animals were killed, 4, 8, and 12 h after the injection of EGF; comparable control groups were injected only with the carrier substance. Thirty minutes before sacrifice, each mouse was injected ip with 24 muCi [3H]thymidine. Incorporation of [3H]-thymidine into the DNA of the tongue, esophagus, and stomach was determined. The results demonstrate for the first time that EGF has a strong in vivo stimulatory effect on DNA synthesis in the tongue, esophagus, and stomach (studies on other areas of the gut have not yet been completed). Under the conditions of the study, stimulatory effects occurred as soon as 4 h subsequent to injection; however, maximal stimulation occurred for all three tissues 8 h after injection. Twelve hours after injection, the levels of DNA synthesis in all tissues were generally returning to normal levels found in the control animals. The results suggest circadian variation in susceptibility to EGF in the different tissues.

Identification and expression of scavenger receptor SR-BI in endothelial cells and smooth muscle cells of rat aorta in vitro and in vivo.

In this study, we used immunoelectron microscopy to investigate the subcellular localization of scavenger receptor class B type I (SR-BI) in the arterial walls of rats. The expression of SR-BI in cultured endothelial and smooth muscle cells of rat aorta after exposure to high-density lipoprotein (HDL) was also investigated by immunofluorescence microscopy and immunoblotting analysis. A peptide containing residues 495-509 from mouse SR-BI (mSR-BI) plus an NH2-terminal cysteine was coupled to hemocyanin to generate mSR-BI antiserum in rabbits. Reactivity of antiserum against the synthetic peptides was confirmed with an enzyme-linked immunosorbent assay (ELISA). The results showed that SR-BI was specifically localized on the surface of the endothelial cells and smooth muscle cells. SR-BI was also observed in the cytoplasm of smooth muscle cells. Immunoblotting analysis indicated that SR-BI was expressed in the cell membrane. The levels of SR-BI increased gradually from 1 to 3 h and decreased at 24 and 48 h after cholesterol-loaded cells were incubated in the culture medium containing HDL. We conclude that SR-BI, a functional receptor for HDL, is expressed in the aortic endothelial cells as well as in smooth muscle cells. This receptor also responds to the presence of HDL in the culture medium.