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Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

Aims This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients. Methods and results This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16–32. Conclusions According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results.

Background: Cardiovascular events, including pericarditis, myocarditis, and myocardial ischaemia, have been reported as complications following COVID-19 vaccination. Case summary: A 28-year-old Japanese woman diagnosed 10 years earlier with systemic lupus erythematosus and antiphospholipid syndrome was admitted to our hospital because of chest pain and Raynaud’s phenomenon. She had received a second dose of the COVID-19 BNT162b2 mRNA vaccine 28 days earlier. 123I-β-methyl iodophenyl pentadecanoic acid (BMIPP) and 201thallium dual myocardial single-photon emission computed tomography demonstrated mildly reduced perfusion of BMIPP in the mid-anterior wall of the left ventricle. Coronary angiography revealed normal coronary arteries; additionally, an endomyocardial biopsy was performed. Histopathological evaluation revealed a normal myocardium without cell infiltration. However, immunostaining for the severe acute respiratory coronavirus (SARS-CoV)/severe acute respiratory coronavirus 2 (SARS-CoV-2) spike protein was positive in the small intramural coronary arteries. The administration of azathioprine (50 mg/day) and amlodipine (5 mg/day) and increases in her prednisolone (10 mg/day) and aspirin doses led to improvements in the symptoms of the patient. Discussion: Our data lead us to speculate that two events in the timeline of the patient, namely, receiving COVID-19 vaccination and the presence of SARS-CoV/SARS-CoV-2 spike protein in small intramural coronary arteries, may be related to the myocardial microangiopathy observed in this patient., European Heart Journal - Case Reports, 7(3), art. no. ytad102; 2023

Background Klotho, which was originally identified as an aging suppressor, is a key regulator of bone and mineral metabolism. Transmembrane and soluble forms of Klotho protein have been identified. The transmembrane form serves as an obligate co-receptor for fibroblast growth factor 23 (FGF23). However, the physiological importance of soluble form of Klotho has not been determined. Purpose The present study aimed to test the hypothesis that circulating soluble Klotho levels can predict the presence or extent of coronary artery calcification (CAC) in patients with coronary artery disease. Methods We analyzed CAC of culprit lesions in patients with 75 stable angina pectoris who were not on dialysis and were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). Arc and length of each calcium within the culprit lesion was measured by IVUS. The main outcome measure was the calcium index; a volumetric IVUS-derived measure which was calculated as total calcium length/lesion length × maximal calcium arc/360°. Low calcium index was defined as calcium index 460 pg/mL). Results Compared with patients with low-Klotho, those with high-Klotho had higher estimated glomerular filtration rate (eGFR) (69±20 vs. 55±16 mL/min/1.73 m2, p Conclusions Serum Klotho values were independently and inversely associated with the degree of CAC assessed by IVUS. These findings have important clinical implications for serum Klotho as a biomarker that reflects the extent of CAC.

RNA polymerase from cells of the deep-sea bacterium Shewanella violacea DSS12 was purified using three chromatographic steps. An in vitro transcription assay indicated that the purified enzyme was sigma(70) containing RNA polymerase. The enzyme activity was inhibited in the presence of rifampicin when the sensitive domain was targeted. The rpoBC genes encoding for the beta and beta' subunits of RNA polymerase were cloned and their nucleotide sequences determined. Expression plasmids, designated pQSVB and pQSVC, to overproduce these proteins were constructed, and the proteins were purified using a Ni(2+) affinity column. In vitro reconstitution using all proteins for the holoenzyme (alpha, beta, beta', sigma(70)) was carried out and the activity of the recombinant RNA polymerase was detected.

C-Mannosylation is a novel type of glycosylation in proteins. There are several examples of proteins in which the specific motif Trp-X-X-Trp is mannosylated at the first Trp to produce C-mannosylated Trp (CMW). Although C-mannosylation modifies Trp-X-X-Trp, predicted to be a functional motif of various integral proteins such as cytokine receptors, the physiological or pathological relevance of C-mannosylation in the cell is still not known. In this study, to characterize C-mannosylation in biological samples, we generated specific polyclonal antibodies against CMW by using a chemically synthesized CMW as an antigen. Using the antibody, we investigated the effect of hyperglycemic conditions on protein C-mannosylation in cultured cells and diabetic Zucker fatty rats. We found that protein C-mannosylation was increased in macrophage-like RAW264.7 cells under hyperglycemic conditions compared to low-glucose conditions. Furthermore, C-mannosylation was increased in the aortic vessel wall of Zucker fatty rats. Thrombospondin-1 was identified as a protein modified with C-mannosylation, and its expression was also increased in the aortic tissues of Zucker fatty rats. These results indicate that C-mannosylation is increased in specific tissues or cell types under hyperglycemic conditions, suggesting a pathological role for the increased C-mannosylation in the development of diabetic complications.

The method of electrophoretic mobility shift assay under high-pressure conditions was improved using a high-pressure electrophoresis apparatus with capillary narrow-tube gel. It was found that the protein-DNA complex in the gel was stained as a high-resolution spot with ethidium bromide. Using this method, it was found that the behavior under high-pressure conditions of the protein-DNA complex composed of NtrC protein and its target promoter DNA is important for the pressure-regulated transcription process, and it was confirmed that the complex was dissociated above a pressure of 70 MPa.

Purpose: Percutaneous Coronary Intervention (PCI) is often complicated by peri-Procedural Myocardial Injury (PMI) as manifested by cardiac troponin elevation, which is associated with increased cardiac events. However, the method of prediction for PMI has not been established. The purpose of the present study was to investigate whether plaque composition analysis by iMap-Intravascular Ultrasound (iMap-IVUS), a novel radiofrequency intracoronary imaging system, can predict the PMI assessed by high-sensitive cardiac troponin T (hs-TnT). Methods: Forty-five culprit plaques in patients with stable angina pectoris, whose hs-TnT levels before PCI were normal, were imaged using iMap-IVUS before PCI. Volumetric iMap-IVUS analysis was performed across the entire lesion segment, and cross-sectional area analysis was performed at the minimum lumen site. The iMap-IVUS analysis classified tissue characteristics into 4 major components including fibrotic, lipidic, necrotic, and calcified. Those were reported in absolute amounts and as a percentage of plaque area or volume. The hs-TnT was measured before and within 24 hours after PCI, and their differences were expressed as Δhs-TnT. The PMI was defined as hs-TnT elevation after PCI of >5× upper limit level. Results: Of the 45 patients, the PMI was observed in 13 patients (29%) after PCI. The absolute and percent necrotic areas (6.9±3.7 vs. 4.1±2.7 mm2, p=0.007, and 51±12 vs. 34±15%, p=0.001) and the absolute and percent necrotic volumes (50.5±31.2 vs. 28.6±21.3 mm3, p=0.015, and 43±13 vs. 27±11%, p=0.001, respectively) were significantly greater, and the percent fibrotic areas and volumes (36±12 vs. 53±17%, p=0.002, and 45±13 vs. 61±13%, p=0.002, respectively) were significantly smaller in patients with PMI compared with those without PMI. The Δhs-TnT correlated positively with absolute and percent necrotic area and volume, lesion length, remodeling index, stent length, and negatively with absolute and percent fibrotic area and volume. Multivariate logistic regression analysis showed that percent necrotic volume was the only independent predictor of the PMI (odds raio, 1.11; 95% CI, 1.03–1.20; p=0.005). The area under the receiver-operator characteristic curve for percent necrotic volume predicting the PMI was 0.81. The optimal cut-off value of percent necrotic volume for predicting the PMI was 40% (sensitivity 73%, specificity 79%). Conclusions: Plaque composition analysis by iMap-IVUS shows that the PMI often occurs in lesions with large necrotic volumes.

Purpose: The iMap-intravascular ultrasound (iMap-IVUS), a novel radiofrequency intracoronary imaging system, can generate objective and quantitative information about coronary plaque compositions. The aim of this study was to determine whether iMap-IVUS can detect Thin-Cap Fibroatheroma (TCFA), which is a primary type of vulnerable plaque, as determined by Optical Coherence Tomography (OCT). Methods: Seventy nine culprit plaques in 70 patients with stable and 9 with unstable angina pectoris were analyzed using iMap-IVUS and OCT. Quantitative volumetric grayscale and iMap-IVUS analysis was performed across the entire lesion segment, and cross-sectional area analysis was performed to evaluate vessel remodeling. Plaque compositions were classified using iMap-IVUS as fibrotic, lipidic, necrotic and calcified, which are expressed as absolute amounts and as a percentage of plaque volume. We defined OCT-derived TCFA as lipid-rich plaque with a