Generic substitution of amlodipine is not associated with increased risk of mortality or adverse cardiovascular events: An observational cohort study.

This study aims to assess clinical outcomes following switching from originator to generic amlodipine. This population-based, matched, cohort study included users of originator amlodipine using claims data during 2018-2020 from a health system in Tianjin, China, in which usage of generic amlodipine was promoted by a drug procurement policy, the national volume-based procurement. Non-switchers refer to those remained on originator after the policy, while pure-switchers were those who switched to and continued using generic amlodipine, and back-switchers were those switched to generic amlodipine but then back to the originator. Propensity score matching generates comparable non-switchers and pure-switchers pairs, and non-switchers and back-switchers pairs. The primary outcome was major adverse cardiovascular events (MACEs), defined as all-cause mortality, stroke, and myocardial infarction during follow-up (April 1, 2019 to December 30, 2020). Secondary outcomes included heart failure, atrial fibrillation, and adherence to amlodipine. The hazard ratio (HR) for each clinical outcome was assessed through Cox proportional hazard regression. In total, 5943 non-switchers, 2949 pure-switchers, and 3061 back-switchers were included (mean age: 62.9 years; 55.5% men). For the matched pairs, pure-switchers (N = 2180) presented no additional risks of clinical outcomes compared to non-switchers (N = 4360) (e.g., MACEs: 2.86 vs. 2.95 events per 100 person-years; HR = 0.97 [95%CI: 0.70-1.33]). Back-switchers (N = 1998) also presented no additional risk compared to non-switchers (N = 3996) for most outcomes except for stroke (HR = 1.55 [95%CI: 1.03-2.34]). Pure-switchers and back-switchers all had better amlodipine adherence than non-switchers. Generic substitution of amlodipine is not associated with increased risk of cardiovascular events or all-cause mortality, but improves medicine adherence.

Role of CCRL2 in the Pathogenesis of Experimental Autoimmune Myocarditis via P21-Activated Kinase 1/NOD-Like Receptor Protein 3 Pathway.

Myocarditis, a severe inflammatory disease, is becoming a worldwide public health concern. This study aims to elucidate the effect of Chemokine (C C motif) receptor-like 2 (CCRL2) in experimental autoimmune myocarditis (EAM) occurrence and its potential regulatory mechanisms.EAM was simulated in a mouse model injected with α-myosin-heavy chain. The changes on EAM were assessed through histological staining of heart tissues, including measuring cardiac troponin I (cTnI), proinflammatory cytokines, transferase-mediated dUTP nick end labeling (TUNEL) assay, and cardiac function. Then, the heart tissues from the EAM mouse model and control groups were analyzed through transcriptome sequencing to identify the differential expressed genes (DEGs) and hub genes related to pyroptosis. Downregulation of CCRL2 further verified the function of CCRL2 on EAM and p21-activated kinase 1/NOD-like receptor protein 3 (PAK/NLRP3) signaling pathways in vivo.The EAM model was constructed successfully, with the heart weight/body weight ratio, serum level of cTnI, and concentrations of proinflammatory cytokines elevation. Moreover, cell apoptosis was also significantly increased. Transcriptome sequencing revealed 696 and 120 upregulated and downregulated DEGs, respectively. After functional enrichment, CCRL2 was selected as a potential target. Then, we verified that CCRL2 knockdown improved cardiac function, alleviated EAM occurrence, and reduced PAK/NLRP3 protein expression.CCRL2 may act as a novel potential treatment target in EAM by regulating the PAK1/NLRP3 pathway.

A pilot clinical assessment of biphasic asymmetric pulsed field ablation catheter for pulmonary vein isolation.

Pulsed field ablation (PFA) is a new treatment for atrial fibrillation (AF), and its selective ablation characteristics give it a significant advantage in treatment. In previous cellular and animal experiments, we have demonstrated that biphasic asymmetric pulses can be used to ablate myocardial tissue. However, small-scale clinical trials are needed to test whether this approach is safe and feasible before extensive clinical trials can be performed. Therefore, the purpose of this experiment is to determine the safety and feasibility of biphasic asymmetric pulses in patients with AF and is to lay the foundation for a larger clinical trial. Ablation was performed in 10 patients with AF using biphasic asymmetric pulses. Voltage mapping was performed before and after PFA operation to help us detect the change in the electrical voltage of the pulmonary veins (PV). 3-Dimensional mapping system showed continuous low potential in the ablation site, and pulmonary vein isolation (PVI) was achieved in all four PV of the patients. There were no recurrences, PV stenosis, or other serious adverse events during the 12 months follow-up. The results suggest that PFA using biphasic asymmetric waveforms for patients with AF is safe, durable, and effective and that a larger clinical trial could begin. Clinical Trial Registration: https://www.chictr.org.cn/, identifier, ChiCTR2100051894.

Ten-year follow-up of very-high risk hypertensive patients undergoing renal sympathetic denervation.

OBJECTIVES: Renal denervation (RDN) has been proven to be effective in lowering blood pressure (BP) in patients, but previous studies have had short follow-ups and have not examined the effects of RDN on major cardiovascular outcomes. This study aimed to demonstrate the effectiveness and safety of RDN in the long-term treatment of hypertension and to determine if it has an effect on cardiovascular outcomes. METHODS: All patients with resistant hypertension who underwent RDN between 2011 and 2015 at Tianjin First Central Hospital were included in the study. Patients were followed up at 1,5 and 10 years and the longest follow-up was 12 years. Data were collected on office BP, home BP, ambulatory BP monitoring (ABPM), renal function, antihypertensive drug regimen, major adverse events (including acute myocardial infarction, stroke, cardiovascular death and all cause death) and safety events. RESULTS: A total of 60 participants with mean age 50.37 ±â€Š15.19 years (43.33% female individuals) completed long-term follow-up investigations with a mean of 10.02 ±â€Š1.72 years post-RDN. Baseline office SBP and DBP were 179.08 ±â€Š22.05 and 101.17 ±â€Š16.57 mmHg under a mean number of 4.22 ±â€Š1.09 defined daily doses (DDD), with a reduction of -35.93/-14.76 mmHg as compared with baseline estimates ( P  < 0.0001). Compared with baseline, ambulatory SBP and DBP after 10-years follow-up were reduced by 14.31 ±â€Š10.18 ( P  < 0.001) and 9 ±â€Š4.35 ( P  < 0.001) mmHg, respectively. In comparison to baseline, participants were taking fewer antihypertensive medications ( P  < 0.001), and their mean heart rate had decreased ( P  < 0.001). Changes in renal function, as assessed by estimated glomerular filtration rate (eGFR) and creatinine, were within the expected rate of age-related decline. No major adverse events related to the RDN procedure were observed in long-term consequences. All-cause mortality and cardiovascular mortality rates were 10 and 8.34%, respectively, for the 10-year period. CONCLUSION: The BP-lowering effect of RDN was safely sustained for at least 10 years post-procedure. More importantly, to the best of my knowledge, this is the first study to explore cardiovascular and all-cause mortality at 10 years after RDN.

Liver transplantation for pediatric patients with congenital heart disease: A single-center study in mainland China.

BACKGROUND: Liver transplantation (LT) is a serious cardiovascular stressor for patients with end-stage liver disease (ESLD). Data on the effects of cardiovascular diseases on pediatric LT is limited. No study on LT for pediatric patients with ESLD combined with congenital heart disease (CHD) has been reported from mainland China. METHODS: A total of 1005 patients were included in this study. The Kaplan-Meier method with log-rank testing was used to evaluate survival outcomes between groups. Univariable and multivariable Cox regression models were used to determine the risk factors for patient and graft survival. RESULTS: The most common indication for LT was biliary atresia (BA 90.3%). The prevalence of CHD was 3.8% (38). 42 CHD were found in 38 patients. The incidence of death and graft loss was more common in the CHD group than in the no-CHD group (13.2% vs. 5.0%, p = .045 and 15.8% vs. 6.2%, p = .019, respectively). The 5-year patient survival and graft survival in the CHD group versus the no-CHD group was 86.8% versus 94.7% (log-rank p = .022) and 84.2% versus 93.5% (log-rank p = .015), respectively. No significant differences were observed in re-transplantation, hepatic artery thrombosis (HAT), and portal vein thrombosis (PVT). After adjusting for age, BMI, etiology of LT, and other confounding factors, we can still find that the presence of CHD was associated with patient and graft survival after LT. CONCLUSION: The presence of CHD was associated with higher mortality and lower graft survival after LT. If possible, the cardiac defects should be addressed prior to LT.

Low Dose of 5-Aminolevulinic Acid Hydrochloride Alleviates the Damage in Cardiomyocytes Induced by Lenvatinib via PI3K/AKT Signaling Pathway.

BACKGROUND: Lenvatinib is an oral tyrosine kinase inhibitor (TKI), and has been applied in the clinical trials for the treatment of hepatocellular carcinoma (HCC). The function of 5-aminolevulinic acid hydrochloride (ALA) treatment in protecting cardiomyocytes under lenvatinib stimulation was investigated. METHODS: H9c2 cells were treated with 2 mg/mL lenvatinib for 48 h and 1 mM ALA in the lenvatinib with low dose 5-aminolevulinic acid treatment group (LL) group, 10 mM ALA in the lenvatinib with high-dose 5-aminolevulinic acid treatment group (LH) group and cells without treatment were used as an internal control. C57/BL mice were treated with 10 mg/kg lenvatinib and 200 mg/kg ALA in the LL group and 400 mg/kg ALA in the LH group by gavage once per day for 4 weeks. The proliferation ability of cells was detected using the methyl thiazolyl tetrazolium (MTT) assay. Target gene expression was calculated through real-time quantitative PCR (qPCR), and target protein expression was calculated through Western blotting analysis. The concentrations of cardiovascular protective factors were detected using enzyme linked immunosorbent assay (ELISA). RESULTS: In these experiments, 10 mM ALA significantly increased the viability rate of cardiomyocytes (105.4 ± 8.0%) compared with the single lenvatinib treatment group (73.2 ± 6.5%). We also noticed that activation of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways were activated after low-dose ALA treatment. 5-ALA treatment led to the downregulation of intercellular cell adhesion molecule-1 (ICAM-1) (0.81- and 0.71-fold), vascular cell adhesion molecule (VCAM) (0.63- and 0.66-fold), angiotensin I (ANGI) (0.88- and 0.66-fold), ANGII (0.66- and 0.48-fold) and upregulation of endothelial nitric oxide synthases (eNOS) (1.25- and 1.89-fold) compared with non 5-ALA treatment group. CONCLUSIONS: With more experiments on animal models, low-dose of ALA treatment might be a therapeutic strategy to alleviate the damage to cardiomyocytes induced by lenvatinib.

2023 Chinese expert consensus on the impact of COVID-19 on the management of cardiovascular diseases.

The primary site of infection in COVID-19 exhibit is the respiratory system, but multiple organ systems could be affected. The virus could directly invade cardiomyocytes. Alternatively, cytokine storm could lead to myocardial injury. More importantly, the management of existing cardiovascular diseases must be re-examined in COVID-19 due to, for example, interaction between antiviral agents and with a wide variety of pharmacological agents. The Branch of Cardiovascular Physicians of Chinese Medical Doctor Association organized a panel of experts in cardiovascular and related fields to discuss this important issue, and formulated the "2023 Chinese Expert Consensus on the Impact of COVID-19 on the Management of Cardiovascular Diseases." The Consensus was drafted on the basis of systematic review of existing evidence and diagnosis and treatment experience, and covers three major aspects: myocardial injury caused by COVID-10 and COVID-19 vaccine, the impact of COVID-19 on patients with cardiovascular disease, and the impact of COVID-19 on the cardiovascular system of healthy people, and rehabilitation guidance recommendations. The Consensus involves 11 core clinical issues, including incidence, pathogenesis, clinical manifestations, treatment strategies, prognosis, and rehabilitation. It is our hope that this Consensus will provide a practical guidance to cardiologists in the management of cardiovascular diseases in the new era of COVID-19 pandemic.

Influencing factors and prognostic value of left ventricular systolic dysfunction in patients with complete occlusion of the left anterior descending artery reperfused by primary percutaneous coronary intervention.

BACKGROUND: The aim of this study was to perform a retrospective analysis of patients with acute anterior wall ST-segment elevation myocardial infarction (AAW-STEMI) whose left anterior descending (LAD) artery was completely occluded and reperfused by primary percutaneous coronary intervention (PPCI) and to determine the influencing factors and prognostic value of left ventricular systolic dysfunction (LVSD) in the acute phase of acute myocardial infarction (AMI). METHODS: A total of 304 patients with AAW-STEMI were selected. The selected patients were divided into two groups: the preserved left ventricular ejection fraction (pLVEF) group (LVEF ≥ 50%, n = 185) and the reduced left ventricular ejection fraction (rLVEF) group (LVEF < 50%, n = 119). The influencing factors of LVSD and their predictive value for LVSD were analyzed. Patients were followed up by examining outpatient records and via telephone. The predictive value of LVSD for the cardiovascular mortality of patients with AAW-STEMI was analyzed. RESULTS: Age, heart rate (HR) at admission, number of ST-segment elevation leads (STELs), peak creatine kinase (CK) and symptom to wire-crossing (STW) time were independent risk factors for LVSD (P < 0.05). The receiver operating characteristic (ROC) analysis showed that the peak CK had the strongest predictive value for LVSD, with an area under the curve (AUC) of 0.742 (CI, 0.687 to 0.797) as the outcome. At a median follow-up of 47 months (interquartile range, 27 to 64 months), the Kaplan‒Meier survival curves up to 6-year follow-up revealed a total of 8 patients succumbed to cardiovascular disease, with 7 (6.54%) in the rLVEF group and 1 (0.56%) in the pLVEF group, respectively (hazard ratio: 12.11, [P = 0.02]). Univariate and multivariate Cox proportional hazards regression analysis demonstrated that rLVEF was an independent risk predictor of cardiovascular death in patients with AAW-STEMI discharged after PPCI (P < 0.01). CONCLUSIONS: Age, HR at admission, number of STELs, peak CK, and STW time may be used to identify patients with a high risk of heart failure (HF) in a timely manner and initiate early standard therapy for incident LVSD in the acute phase of AAW-STEMI reperfused by PPCI. A trend toward increased cardiovascular mortality at follow-up was significantly linked to LVSD.

Subclinical cardiac abnormalities in children with biliary atresia correlate with outcomes after liver transplantation.

Objective: There are subclinical cardiac abnormalities (SCA) in children with biliary atresia (BA). However, data on the consequences of these cardiac changes after liver transplantation (LT) remain controversial in the pediatric field. We aimed to determine the relationship between outcomes and the subclinical cardiac abnormalities in pediatric patients with BA based on two-dimensional echocardiography (2DE) parameters. Methods: A total of 205 children with BA were enrolled in this study. The relationship between 2DE parameters and outcomes, including death and serious adverse events (SAE) after LT, was analyzed by regression analysis. Using receiver operator characteristic (ROC) curves to determine the optimal cut-off values of 2DE parameters for outcomes. Differences in the AUCs were compared using DeLong's test. The Kaplan -Meier method with log-rank testing was used to evaluate survival outcomes between groups. Results: Left ventricular mass index (LVMI) and relative wall thickness (RWT) were found to be independently associated with SAE (OR: 1.112, 95% CI: 1.061 - 1.165, P < 0.001 and OR: 1.193, 95% CI: 1.078 - 1.320, P = 0.001, respectively). The cutoff value of LVMI for predicting the SAE was 68 g/m2.7 (AUC = 0.833, 95% CI 0.727-0.940, P < 0.001), and the cutoff value of RWT for predicting the SAE was 0.41 (AUC = 0.732, 95% CI 0.641-0.823, P < 0.001). The presence of subclinical cardiac abnormalities (LVMI > 68 g/m2.7, and/or RWT > 0.41) was associated with lower patient survival (1-year, 90.5% vs 100.0%; 3-year, 89.7% vs 100.0, log-rank P = 0.001). and higher incidence of SAE events. Conclusions: Subclinical cardiac abnormalities were correlated with post-LT mortality and morbidity in children with BA. LVMI can predict the occurrence of death and serious adverse events after liver transplantation.

Maslinic Acid Ameliorates Myocardial Ischemia Reperfusion Injury-Induced Oxidative Stress via Activating Nrf2 and Inhibiting NF-[Formula: see text]B Pathways.

Maslinic acid (MA) is a pentacyclic triterpene obtained from the peel of olives that exhibits anti-inflammatory and antioxidant properties in several conditions. Our previous study revealed that MA exerted a cardioprotective effect by repressing inflammation and apoptosis during myocardial ischemia-reperfusion injury (MIRI). However, data regarding the antioxidative effects of MA on MIRI remains limited. This study aims to elucidate the antioxidative roles and underlying mechanisms of MA on MIRI. The left anterior descending coronary artery of rats was subjected to ligate for the induction of the ischemia/reperfusion (I/R) model and the H9c2 cells were exposed to hydrogen peroxide (H2O2) to mimic oxidative stress. The results showed that MA reduced the I/R-induced myocardial injury and H2O2-induced cardiomyocyte death in a dose-dependent manner. Meanwhile, MA increased the activities of glutathione and superoxide dismutase both in vitro and in vivo while lowering the levels of reactive oxygen species and malondialdehyde. Mechanistically, MA could facilitate Nrf2 nuclear translocation, activate the Nrf2/HO-1 signaling pathway, and repress the NF-[Formula: see text]B signaling pathway both in I/R- and H2O2-induced oxidative stress. Besides, MA promoted the intranuclear Nrf2 and HO-1 expression, which could in part be improved by QNZ (NF-[Formula: see text]B inhibitor) in H2O2-insulted cells. Conversely, MA markedly reduced the intranuclear NF-[Formula: see text]B p65 and TNF-[Formula: see text] expression, which could be partially abolished by ML385 (Nrf2 inhibitor). Overall, our results indicate that MA, in a dose-dependent manner, mitigated I/R-induced myocardial injury and oxidative stress via activating the Nrf2/HO-1 pathway and inhibiting NF-[Formula: see text]B activation. Furthermore, MA exerts its cardioprotective effect through regulating the crosstalk between the Nrf2 and NF-[Formula: see text]B pathways.

The Relationship between Vascular Aging Phenotypes and Renal Damage among Individuals with Type 2 Diabetes.

OBJECTIVE: The aim of this study was to investigate the relationship between vascular aging (VA) phenotypes and renal damage in type 2 diabetic population. METHODS: In this cross-sectional study, we included 8,141 individuals with type 2 diabetes who participated in the Kailuan Study during 2010-2018 and completed the brachial-ankle pulse wave velocity (baPWV) assessment for arterial stiffness, an indicator for VA. The age- and sex-specific 10th and 90th percentiles of baPWV based on a reference cohort were used as cutoffs to define supernormal VA (SUPERNOVA, baPWV<10th percentiles), normal VA (NVA, baPWV 10th to 90th percentiles), and early VA (EVA, baPWV>90th percentiles). The estimated glomerular filtration rate (eGFR) and proteinuria levels were used to assess renal damage, including isolated proteinuria, isolated kidney function decline (eGFR<60 mL/min/1.73 m2), and proteinuria combined with kidney function decline. Multivariable logistic regression analysis was used to analyze the relationship between VA phenotypes and diabetic kidney damage. RESULTS: The prevalences of isolated proteinuria, isolated kidney function decline, and proteinuria combined with kidney function decline were 17.0%, 12.2%, and 5.4%, respectively. Compared with NVA, SUPERNOVA was associated with 34% lower odds (95% confidence interval [CI]: 0.46-0.96) of isolated proteinuria after adjusting for age, sex, and other potential confounders. EVA was associated with higher odds of all three types of kidney damage; the adjusted odds ratio (95% CI) was 1.42 (1.20-1.67) for proteinuria, 1.24 (1.01-1.51) for kidney function decline, and 1.56 (1.18-2.06) for proteinuria combined with kidney function decline. CONCLUSIONS: VA phenotypes are associated with renal damage, especially isolated proteinuria. SUPERNOVA was associated with lower odds of isolated proteinuria and EVA was associated with higher odds of proteinuria and kidney function decline.

Superior mesenteric artery embolism after radiofrequency ablation in regularly anticoagulated patients with paroxysmal atrial fibrillation: a case report.

BACKGROUND: Superior mesenteric artery embolism (SMAE) is a rare cause of acute abdomen, and the fatality rate is extremely high if it is not diagnosed and treated in time. Due to the lack of knowledge and experience of nonspecialist physicians, it is easy to misdiagnose. Radiofrequency ablation (RFA) has become the first-line treatment strategy for atrial fibrillation (AF). Thromboembolic events are some of the major complications after RFA, whereas SMAE is rarely reported. CASE PRESENTATION: A 70 year-old woman with paroxysmal AF who regularly took anticoagulant drugs for 3 months experienced abdominal pain after RFA. At the outset, she was misdiagnosed as mechanical intestinal obstruction. When the patient presented with blood in the stool, abdominal enhancement computed tomography was conducted and showed a small bowel perforation. Immediate laparotomy was performed, and the final diagnosis was SMAE. CONCLUSION: It is suggested that for unexplained abdominal pain after RFA of AF, the possibility of SMAE should be considered, and a targeted examination should be carried out in time to confirm the diagnosis and give appropriate treatment.

Enhanced stent visualization system for percutaneous coronary intervention in patients with chronic kidney disease: effects on contrast media volume and radiation exposure.

OBJECTIVE: We aimed to assess the impact of using enhanced stent visualization (ESV) systems on contrast media volume and radiation dose in percutaneous coronary intervention (PCI), especially for patients with chronic kidney disease (CKD). BACKGROUND: Coronary heart disease (CHD) is associated with chronic kidney disease (CKD), as they share a similar pathological pathway. In addition, the iodinated contrast media used for angiography is a risk factor for contrast-associated acute kidney injury (CA-AKI), which could aggravate the progression of CKD. We hypothesized that ESV systems have the potential to reduce the use of contrast media as well as the radiation dose; however, few studies have reported the impact on contrast media with the use of ESV systems. METHODS: We retrospectively collected 124 patients with acute coronary syndrome who underwent PCI from May 2020 to July 2021. The patients were divided into the ESV-guided group (n = 64) and angiography-guided group (n = 60). Procedural parameters, including contrast media volume, radiation exposure (in Air Kerma-AK and Dose Area Product-DAP), number of cines, cine frames, fluoroscopy and procedure time, were recorded and analysed. RESULTS: The groups were comparable regarding the patient characteristics. There was a significant reduction in contrast media volume (174.7 ± 29.6 ml vs.132.6 ± 22.3 ml, p = 0.0001), radiation exposure (776 (499 - 1200) mGy vs. 1065 (791 - 1603) mGy, p = 0.002 in AK; 43 (37 - 73) Gycm2 vs. 80 (64 - 133) Gycm2, p = 0.030 in DAP) and procedure time (53.06 ± 21.20 min vs. 72.00 ± 30.55 min, p = 0.01) with the use of ESV systems. Similar results were observed in the subgroup analysis for the patients with CKD. CONCLUSION: This study suggested that the use of ESV is associated with reduced contrast media usage, radiation dose and procedure time during PCI. The same results were observed in a subgroup analysis in patients with CKD, and this shows that ESV-guided PCI has the potential to reduce renal impairment and mitigate the progression of CKD for those CHD patients with CKD.

Molecular mechanisms and effects of urocortin II on rat adventitial fibroblast calcification induced by calcified medium.

The present study aimed to assess the role of urocortin II (UII) in the process of vascular calcification in vitro by using a calcification model, to detect the changes in the mRNA and protein levels of associated markers in rat adventitial fibroblasts (AFs) during their phenotypic transformation to osteoblast cellsto clarify the main signal transduction pathway of UII responsible for regulating vascular calcification and AF phenotypic transformation of osteoblast cells, and to prove that UII was an endogenous factor promoting vascular calcification, so as to provide an effective experimental basis for the clinical regulation of related diseases caused by vascular calcification. Finally, we successfully constructed the calcified cell model, found that UII was an endogenous substance regulating vascular calcification, regulated the vascular calcification by promoting apoptosis and inhibiting autophagy through up- and downregulated BAX and BCL-2/BECLIN 1 (BECN1) level, and the Wnt/ß-catenin signaling pathway was involved.

Renal Denervation Reduces Blood Pressure and Improves Cardiac Function: Results from a 12-Month Study.

Background: Previous studies showed that a decline in BP can reverse pressure-overloaded left ventricular hypertrophy in the long term. Whether this structural remodeling and improved cardiac function were due to reduced BP levels or sympathetic tone is unclear. The aim of this study was to evaluate the efficacy of renal denervation (RDN) on cardiac function and left ventricular hypertrophy in patients diagnosed with resistant hypertension with systolic and diastolic dysfunction. Methods: Thirteen patients diagnosed with resistant hypertension underwent bilateral RDN (RDN group), and 13 patients were selected as the control group (drug group) who received regular antihypertensive drugs for the first time. Demographic analysis and hematologic tests were performed to determine renal function as well as BNP levels. Echocardiogram was performed at baseline and 12 months after RDN. Results: All the baseline characteristics are comparable in two groups. Both RDN and drug regiments resulted in significant reduction from baseline in SBP/DBP at 12-month follow-up (all P values < 0.01), and the decline due to two interventions showed no statistically significant difference (F = 1.64, P = 0.213 and F = 0.124, P = 0.853 for SBP and DBP, respectively). RDN significantly reduced mean LV mass index (LVMI) from 151.43 ± 46.91 g/m2 to 136.02 ± 37.76 g/m2 (P = 0.038) and ejection fraction (LVEF) increased from 57.15 ± 5.49% at baseline to 59.54 ± 4.18% at 12 months (P = 0.039). No similar changes were detected in the drug group (P values, 0.90 for EF and 0.38 for LVMI). Renal parameters including BUN, Cr, UA, and eGFR at baseline, 3 months, and 12 months showed no marked difference (P = 0.497, 0.223, 0.862, 0.075, respectively). Conclusions: Our findings show that in addition to hypertension and its progression, elevated sympathetic hyperactivity is related to left ventricular hypertrophy and cardiac function.

A ROS-Responsive Simvastatin Nano-Prodrug and its Fibronectin-Targeted Co-Delivery System for Atherosclerosis Treatment.

Nanoprodrugs with responsive release properties integrate the advantages of stimuli-responsive prodrugs and nanotechnology. They would provide ultimate opportunity in fighting atherosclerosis. In this study, we synthesized a redox-responsive nanoprodrug of simvastatin (TPTS) by conjugating α-tocopherol polyethylene glycol derivative to the pharmacophore of simvastatin with a thioketal linker. TPTS formed nanoparticles and released parent simvastatin in the presence of hydrogen peroxide. Moreover, by taking advantage of the self-assembly behavior of TPTS, we developed a fibronectin-targeted delivery system (TPTS/C/T) to codelivery simvastatin prodrug and ticagrelor. In vitro and in vivo experiments indicated that TPTS and TPTS/C/T had good stability, which could reduce off-target leakage of drugs. They greatly inhibited the M1-type polarization of macrophages; reduced intracellular reactive oxygen species level and inflammatory cytokine; and TNF-α, MCP-1, and IL-1ß were secreted by macrophage cells, thus providing enhanced anti-inflammatory and antioxidant effects compared with free simvastatin. TPTS/C/T realized targeted drug release to plaques and synergistic therapeutic effects of simvastatin and ticagrelor on atherosclerosis treatment in an ApoE-/- mouse model, resulting in excellent atherosclerosis therapeutic efficacy and a promising biosafety profile. Therefore, this study provides a new method for manufacturing statin nanodrugs and a new design idea for related responsive drug release nanosystems for atherosclerosis.

Colchicine-Containing Nanoparticles Attenuates Acute Myocardial Infarction Injury by Inhibiting Inflammation.

PURPOSE: Anti-inflammatory therapy is important for reducing myocardial injury after acute myocardial infarction (MI). New anti-inflammatory drugs and their mechanism are necessary to be explored to improve clinical efficacy. We aimed to improve the efficacy of colchicine on attenuating MI injury by nano-drug delivery systems and to investigate the mechanism of anti-inflammatory. METHODS: A colchicine-containing delivery system based on calcium carbonate nanoparticles (ColCaNPs) was synthesized. The protection against MI by ColCaNPs was evaluated using an in vivo rat model established by ligating the left anterior descending coronary artery. Macrophage polarization and the levels of inflammatory cytokines were determined using immunohistochemistry, Western blot, and ELISA analysis. RESULTS: ColCaNP treatment showed about a 45% reduction in myocardial infarct size and attenuating myocardial fibrosis compared with groups without drug intervention after MI. Furthermore, ColCaNPs significantly decreased the levels of CRP, TNF-α, and IL-1ß in serum and the expression of proinflammatory cytokine in myocardial tissues after MI (p < 0.05). We also found that ColCaNPs notably restrained pyroptosis and inhibited inflammatory response by modulating on M1/M2 macrophage polarization and suppressing TLR4/NFκB/NLRP3 signal pathway. CONCLUSION: Colchicine-containing nanoparticles can protect against MI injury in a clinically relevant rat model by reducing inflammation. In addition, calcium carbonate nanoparticles can increase the cardioprotective effects of colchicine.