Laparoscopic surgery for ectopic pregnancy: A comparative study on the clinical benefits and impact on tubal patency and reproductive outcomes.

BACKGROUND: Ectopic pregnancy is a major contributor to maternal morbidity and mortality across the globe. OBJECTIVE: This study aims to investigate the clinical benefits of laparoscopic surgery in treating ectopic pregnancy, and its impact on tubal patency and reproductive outcomes. METHODS: A clinical study was conducted to compare laparoscopic and medical conservative treatment for ectopic pregnancy. A total of 206 patients were treated for ectopic pregnancy at our hospital from January 2018 to June 2020. Among them, 46 underwent laparoscopic ipsilateral salpingectomy, 54 underwent laparoscopic ipsilateral salpingostomy with lesion removal, and 106 were treated conservatively with medication. RESULTS: The age range and average age of each group are provided, with no significant differences in these general demographic characteristics (p> 0.05). Both the salpingostomy and medication groups had higher rates of ectopic pregnancy compared to the salpingectomy group, with statistically significant differences (p< 0.05). The comparison of ectopic pregnancy rates between the salpingostomy and medication groups showed no significant difference. Within three years, the salpingostomy group had 10 cases of recurrent ectopic pregnancy, with 2 cases on the same side, while the medication group had 18 cases, with 8 cases on the same side. At 3 months after the normalization of blood ß-HCG, the salpingostomy group showed 43 cases of tubal patency (patency rate: 79.63%), while the medication group showed 57 cases (patency rate: 53.77%), with a statistically significant difference between the two groups (p= 0.01). CONCLUSION: Laparoscopic surgery for ectopic pregnancy offers significant clinical benefits over conservative medical treatment, including higher rates of tubal patency and improved reproductive outcomes. These findings support laparoscopic surgery as an effective approach for the management of ectopic pregnancy.

Comparison between a dedicated stent positioning system and conventional stenting of aorto-ostial lesions: a prospective, multi-center, randomized controlled study.

Background: The accurate placement of stents for treatment of coronary aorto-ostial lesions (AOLs) is technically challenging. The purpose of this study was to evaluate the efficacy and safety of a stent positioning system with a dedicated nitinol device and compare them with those of the conventional approach for stenting of coronary AOLs. Methods: In this prospective, multi-center, open-label, randomized study, conducted from November 2015 to April 2019, patients with coronary AOLs that underwent percutaneous coronary intervention (PCI) were randomly allocated (allocation ratio 1:1) using block randomization method to either a stent positioning system group or a conventional technique group. The primary endpoint was the range of stent slippage when positioning. The following secondary endpoints were applied: (I) the extent of swing of the guiding catheters during stent positioning; (II) the rate of accurate stent placement; (III) the procedure time; and (IV) the incidence of major adverse cardiovascular events (MACEs) including cardiac death, myocardial infarction, target lesion revascularization, and stent thrombosis. Results: During the study period, 139 patients with aorto-ostial coronary artery stenosis were included at 5 centers. A total of 69 patients were allocated to the stent positioning system group and 70 patients to the conventional technique group. Angiographic and clinical success were achieved in 100% of the patients included in both groups. The range of stent slippage was significantly shorter in the stent positioning system group than it was in the conventional technique group [0.64 (0.22; 1.35) vs. 1.11 (0.48; 1.72) mm, P=0.01]. The rate of accurate placement of stents was higher in the stent positioning system group than it was in the conventional technique group (74.6% vs. 57.1%, P=0.03). The extent of guiding catheter swing during the stent positioning [0.24 (0.19; 0.53) vs. 0.23 (0.19; 0.53) mm; P=0.95] and the MACEs rates (1.4% vs. 2.9%, P>0.99) were similar between the 2 groups. The procedural time of the stent positioning system was longer than that of the conventional approach [1.00 (0.50; 1.50) vs. 0.80 (0.50; 1.50) min, P=0.09]. Conclusions: The dedicated stent positioning system was is safer and provides more accurate placement of stents for coronary AOLs than the conventional approach, and the associated prolongation of procedure time is insignificant. Trial Registration: Chinese Clinical Trial Registry (ChiCTR), Unique identifier: ChiCTR2100053869. URL: https://www.chictr.org.cn/showproj.html?proj=133280.

Thrombospondin-2 is upregulated in patients with aortic dissection and enhances angiotensin II-induced smooth muscle cell apoptosis.

Thrombospondin-2 (TSP-2) is an important extracellular matrix protein that is involved in a variety of cardiovascular diseases, including viral myocarditis and abdominal aortic aneurysm. The present study aimed to investigate TSP-2 expression in patients with aortic dissection (AD). Aortas were obtained from patients with AD and healthy donors, and TSP-2 expression level in all samples was measured by western blotting and immunofluorescence assays. Blood samples were also collected from patients with AD and non-AD (NAD) subjects. Circulating TSP-2, tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in each sample were detected using ELISAs. In addition, the effect of TSP-2 on angiotensin II (Ang II)-induced smooth muscle cell (SMC) apoptosis was assessed in vitro. Compared with healthy donors, aortic TSP-2 expression level was significantly increased in patients with AD. Furthermore, TSP-2 was secreted primarily by SMCs, but also by endothelial cells. TSP-2 plasma expression level was also elevated in patients with AD compared with non-AD subjects. Furthermore, TSP-2 serum expression level was positively correlated with TNF-α and IL-6 expression levels in patients with AD. In addition, recombinant mouse TSP-2 treatment increased Bax mRNA expression and decreased Bcl2 mRNA expression in Ang II-treated SMCs; however, the effects were reversed following treatment with the NF-κB p65 signaling pathway inhibitor JSH-23 or with the anti-TNF-α and anti-IL-6 neutralizing antibodies. The present study demonstrated that TSP-2 expression was increased in the aortic tissues and plasma of patients with AD. These findings suggested that TSP-2 may participate in the progression of AD by activating the NF-κB p65 signaling pathway and amplifying the inflammatory response.

IL-19 as a Biomarker for the Severity of Acute Myocardial Infarction.

BACKGROUND: Interleukin-19 (IL-19) has been shown to be involved in coronary artery diseases and atherosclerosis, while its expression in myocardial infarction is poorly understood. In this study, the dynamic increase in circulating IL-19 in acute ST-segment elevation myocardial infarction (STEMI) patients was detected. METHOD: Both plasma IL-19 levels and IL-19 mRNA expression in peripheral blood mononuclear cells (PBMCs) from STEMI patients and chest pain syndrome (CPS) patients were detected at different time points, including 1 d, 3 d, 7 d and 14 d after treatment and on admission. RESULTS: Compared with the CPS patients, IL-19 levels and IL-19 gene expression were significantly increased in STEMI patients and peaked at 1 d. From 1-14 d, refocusing treatment, including emergency percutaneous coronary intervention (PCI) and thrombolysis, markedly reduced IL-19 expression and promoted its recovery; of the treatments, the effect of emergency PCI was most significant. In addition, similar trends were also observed with cTnI, NT-proBNP and C-reactive protein (CRP) levels. Furthermore, correlation analysis showed that IL-19 levels were positively correlated with cTnI, NT-proBNP, CRP levels and left ventricular ejection fraction (LVEF) in STEMI patients. CONCLUSIONS: IL-19 is correlated with the severity of acute myocardial infarction, which may be a new idea for the clinical treatment of myocardial infarction.

High-dose nitrate therapy recovers the expression of subtypes α1 and ß-adrenoceptors and Ang II receptors of the renal cortex in rats with myocardial infarction-induced heart failures.

BACKGROUND: Few studies examined the effect of long-acting nitrates on renal function in chronic heart failure (CHF). Thus, we aimed to investigate the effect of long-acting nitrate on the expression of adrenoceptors (AR) and angiotensin II receptor (ATR) subtypes of the renal cortex, in rats with myocardial infarction-induced CHF. METHODS: Rats were randomly divided into the following groups: control, sham-operated, CHF, low- and high-dose nitrate, positive drug control (olmesartan), and high-dose of long-acting nitrate + olmesartan. Ultrasound echocardiography markers were compared, and the levels of AR subtypes, AT1R, and AT2R were measured using reverse transcription-polymerase chain reaction and western blot analysis. Histopathology of the kidney was determined on hematoxylin and eosin-stained sections. RESULTS: CHF significantly increased plasma renin activity (PRA) and angiotensin II levels, upregulated AT1R expression and downregulated α1A-, ß1-, ß2-AR, and AT2R expression compared to the sham control. High-dose nitrate or olmesartan alone, and especially in combination, decreased the levels of PRA and angiotensin II and downregulated the CHF-induced expression of AT1R, α1A-, ß1-, and ß2-AR, and AT2R. CHF resulted in significant impairment of the renal tissue, including inflammatory cells infiltration to the tubular interstitium and surrounding the renal glomerulus, and tubular necrosis, which was alleviated in all treatment groups to different degrees. CONCLUSIONS: Long-acting nitrates could reverse CHF-induced changes in AR and ATR subtypes in the kidney, and improve cardiac function to protect renal function. Compared with monotherapy, the combination of nitrates and olmesartan shows more significant benefits in regulating AR and ATR subtypes.

Relationship of left ventricular thrombus formation and adverse outcomes in acute anterior myocardial infarction in patients treated with primary percutaneous coronary intervention.

BACKGROUND: The incidence of left ventricular thrombus (LVT) is 4% to 15% in patients with anterior acute ST-segment elevation myocardial infarction (ant-AMI) in the era of primary percutaneous coronary intervention (PPCI). And patients with LVT have higher in-hospital mortality. HYPOTHESIS: There is a relationship between LVT formation and 1-year major adverse cardio-cerebrovascular events (MACCE) in patients with ant-AMI treated by PPCI. METHODS: Our study population included 1488 consecutive patients with ant-AMI. The primary endpoint was the incidence of MACCE within 1 year after AMI. The secondary endpoint was the thrombosis disappearance. RESULTS: A total of 106 (7.1%) patients were diagnosed with LVT and 1382 (92.9%) patients without LVT. Patients with LVT had a higher incidence of MACCE than in patients without LVT (21.7%vs10.3%; P < 0.001). Univariate analysis showed LVT was associated with an increase in MACCE risk (odds ratio [OR] = 2.40; 95% confidence interval [CI] [1.37-4.21]; P < 0.001). When examining MACCE components individually, LVT was only associated with the incidence of congestive heart failure (OR = 2.41; 95% CI [1.29-4.58]; P = 0.001). After adjustment for principal confounders, LVT remained an independent risk factor for MACCE (HR = 2.28; 95% CI [1.12-6.38]; P = 0.020). Other independent predictors include 24-hour LVEF, creatine kinase peak value, and age. Further analysis found patients with LVT in international normalized ratio (INR) ≥ 2 group had lower MACCE risk and higher thrombus disappearance than in INR < 2 group (13.5%vs29.6%; P = 0.044; 90.4%vs74.1%; P = 0.029). CONCLUSION: For patients with ant-AMI treated by PPCI, LVT is an independent predictor of 1-year MACCE events. Treatment with vitamin K antagonist in the therapeutic range (INR ≥ 2) has the potential to reduce MACCE risk and promote disappearance of thrombus.

Optimal timing of staged percutaneous coronary intervention in ST-segment elevation myocardial infarction patients with multivessel disease.

BACKGROUND: Studies have shown that staged percutaneous coronary intervention (PCI) for non-culprit lesions is beneficial for prognosis of ST-segment elevation myocardial infarction (STEMI) patients with multivessel disease. However, the optimal timing of staged revascularization is still controversial. This study aimed to find the optimal timing of staged revascularization. METHODS: A total of 428 STEMI patients with multivessel disease who underwent primary PCI and staged PCI were included. According to the time interval between primary and staged PCI, patients were divided into three groups (≤ 1 week, 1-2 weeks, and 2-12 weeks after primary PCI). The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal re-infarction, repeat revascularization, and stroke. Cox regression model was used to assess the association between staged PCI timing and risk of MACE. RESULTS: During the follow-up, 119 participants had MACEs. There was statistical difference in MACE incidence among the three groups (≤ 1 week: 23.0%; 1-2 weeks: 33.0%; 2-12 weeks: 40.0%; P = 0.001). In the multivariable adjustment model, the timing interval of staged PCI ≤ 1 week and 1-2 weeks were both significantly associated with a lower risk of MACE [hazard ratio (HR): 0.40, 95% confidence intervals (CI): 0.24-0.65; HR: 0.54, 95% CI: 0.31-0.93, respectively], mainly attributed to a lower risk of repeat revascularization (HR: 0.41, 95% CI: 0.24-0.70; HR: 0.36, 95% CI: 0.18-0.7), compared with a strategy of 2-12 weeks later of primary PCI. CONCLUSIONS: The optimal timing of staged PCI for non-culprit vessels should be within two weeks after primary PCI for STEMI patients.

Aspirin inhibits growth and enhances cardiomyocyte differentiation of bone marrow mesenchymal stem cells.

This study aimed to examine the effects of aspirin on the growth and cardiomyocyte differentiation grade of bone marrow mesenchymal stem cells (BMMSCs). BMMSCs were divided into five differentiation groups with different concentrations of aspirin (0 mM, 0.5 mM, 1 mM, 2 mM, or 5 mM), and a undifferentiated control group. Cell growth was measured by cell proliferation, apoptosis assays and DNA cycle analysis. The differentiation grade of BMMSC-derived cardiomyocyte-like cells was examined by measuring the levels of cardiac-specific proteins with cyto-immunofluorescence staining, flow cytometry, and Western blotting. Electrophysiological analyses were performed by patch-clamp experiments and calcium transients were measured by a laser scanning confocal microscope. Cell proliferation decreased as the concentration of aspirin increased. Cell apoptosis increased with increasing aspirin concentration. DNA replication was inhibited in the high dose-aspirin group compared to the low dose- or non-aspirin groups. The number of α-myosin heavy chain (α-MHC) and cardiac troponin I (cTnI) positive cells, cardiac troponin T (cTnT) and connexin 43 (Cx43) positive rates, expression levels of Cx43, Nkx2.5, GATA4 and ß1 adrenoceptor increased with increasing aspirin concentration. No sarcomeric cross-striations, spontaneous or induced beating activity or action potentials was observed in each group. Calcium transients were measured in small number cells in 2 mM aspirin group, but the features are atypical. Consequently, aspirin inhibits proliferation and survival of BMMSCs and enhances cardiomyocyte differentiation of BMMSCs.

Human epicardial adipose tissue-derived and circulating secreted frizzled-related protein 4 (SFRP4) levels are increased in patients with coronary artery disease.

BACKGROUND: Previous studies have demonstrated that secreted frizzled-related protein 4 (SFRP4) is associated with impaired glucose and triglyceride metabolism in patients with stable coronary artery disease. In the present study, we investigated human epicardial adipose tissue (EAT)-derived and circulating SFRP4 levels in patients with coronary artery disease (CAD). METHODS: Plasma samples and adipose biopsies from EAT and subcutaneous adipose tissue (SAT) were collected from patients with CAD (n = 40) and without CAD (non-CAD, n = 30) during elective cardiac surgery. The presence of CAD was identified by coronary angiography. SFRP4 mRNA and protein expression levels in adipose tissue were detected by quantitative real-time PCR and immunohistochemistry, respectively. Plasma SFRP4 concentrations were measured by an enzyme-linked immunosorbent assay (ELISA). Correlation analysis and multivariate linear regression analysis were used to determine the association of SFRP4 expression with atherosclerosis as well as clinical risk factors. RESULTS: SFRP4 mRNA and protein expression levels were significantly lower in EAT than in paired SAT in patients with and without CAD (all P < 0.05). Compared to non-CAD patients, CAD patients had higher SFRP4 expression levels in EAT (both mRNA and protein levels) and in plasma. Multivariate linear regression analysis showed that CAD was an independent predictor of SFRP4 expression levels in EAT (beta = 0.442, 95% CI 0.030-0.814; P = 0.036) and in plasma (beta = 0.300, 95% CI 0.056-0.545; P = 0.017). SAT-derived SFRP4 mRNA levels were independently associated with fasting insulin levels (beta = 0.382, 95% CI 0.008-0.756; P = 0.045). In addition, plasma SFRP4 levels were positively correlated with BMI (r = 0.259, P = 0.030), fasting insulin levels (r = 0.306, P = 0.010) and homeostasis model assessment of insulin resistance (HOMA-IR) values (r = 0.331, P = 0.005). CONCLUSIONS: EAT-derived and circulating SFRP4 expression levels were increased in patients with CAD. EAT SFRP4 mRNA levels and plasma SFRP4 concentrations were independently associated with the presence of CAD.

Triiodo-L-Thyronine Promotes the Maturation of Cardiomyocytes Derived From Rat Bone Marrow Mesenchymal Stem Cells.

Bone marrow mesenchymal stem cells (BMMSCs) can differentiate into cardiomyocytes and be used in cardiac tissue engineering for heart regeneration. However, the effective clinical application of cardiomyocytes derived from BMMSCs is limited because of their immature phenotype. The aim of this study was to investigate the potential of triiodo-L-thyronine (T3) to drive cardiomyocytes derived from BMMSCs to a more mature state. BMMSCs were divided into 3 groups: untreated controls, differentiated, and T3 treated. The differentiation potential was evaluated by immunofluorescence microscopy and flow cytometry. Data were represented as the numbers of cells positive for the troponin I (cTnI), α-actinin, GATA4, and the connexin-43 (Cx-43). The mRNA levels of these specific markers of cardiomyocytes were determined by quantitative real-time polymerase chain reaction. The levels of cardiomyocytes markers protein and octamer-binding transcription factor 4 (Oct-4) were determined by Western blot analyses. Our data demonstrate that T3 treatment leads to a significant increase in cells positive for cTnI, GATA4, Cx-43, and α-actinin. The mRNA and protein expression levels of these specific markers of cardiomyocytes were also increased after T3 treatment. At the same time, the protein expression level of Oct-4 was substantially downregulated in T3-treated cells. These results demonstrate that T3 treatment increases the differentiation of BMMSCs induced to cardiomyocytes and promotes their maturation.

Differentiation of Bone Marrow Mesenchymal Stem Cells to Cardiomyocyte-Like Cells Is Regulated by the Combined Low Dose Treatment of Transforming Growth Factor-ß1 and 5-Azacytidine.

Bone marrow mesenchymal stem cells (BMMSCs) are used in cardiac tissue engineering for the regeneration of diseased hearts. We examined the differentiation of rat BMMSCs into cardiomyocyte-like cells when induced with a combined low dose treatment of transforming growth factor-ß1 (TGF-ß1) and 5-azacytidine (5-AZA). Results showed that cell proliferation in the combined low dose treatment group of TGF-ß1 and 5-AZA was increased compared with the TGF-ß1 group or the 5-AZA group. The cell apoptosis was relieved by combined TGF-ß1 and 5-AZA treatment compared to 5-AZA treatment alone. The number of cells positive for myosin heavy chain, connexin-43, α-actin, and troponin I in the combined treatment group was higher than those observed in the TGF-ß1 group or the 5-AZA group. Moreover, the combined low dose treatment group of TGF-ß1 and 5-AZA reveals the strongest expression of troponin I, α-actin, and phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ErK1/2) among the treatment groups. These results suggest that the combined low dose treatment of TGF-ß1 and 5-AZA can improve the differentiation potential of rat BMMSCs into cardiomyocyte-like cells and alleviate cell damage effects in vitro. The mechanism that is involved in influencing differentiation may be associated with p-ErK1/2.

Concomitant Retrograde Coronary Venous Infusion of Basic Fibroblast Growth Factor Enhances Engraftment and Differentiation of Bone Marrow Mesenchymal Stem Cells for Cardiac Repair after Myocardial Infarction.

AIM: Basic fibroblast growth factor (bFGF) increases the migration and viability of bone marrow mesenchymal stem cells (MSCs) in vitro. Retrograde coronary venous infusion can provide both increased regional bFGF concentrations and homogeneous cell dissemination. We determined whether retrograde delivery of bFGF enhances the potency of transplanted MSCs for cardiac repair in a canine infarct model. METHODS AND RESULTS: Under hypoxic conditions, cellular migration was significantly increased in MSCs co-cultured with bFGF compared to vascular endothelial growth factor or insulin-like growth factor, and bFGF promoted MSCs differentiation into a cardiomyocyte phenotype. A canine infarct model was employed by coronary ligation. One week later, animals were subjected to retrograde infusion of combination bFGF (200ng/mL) and MSCs (1×10(8) cells) (n=5), MSCs (1×10(8) cells, n=5), bFGF (200ng/mL, n=5), or placebo (phosphate-buffered saline, n=3). Four weeks after infusion, only the bFGF+MSCs therapy exhibited significantly increased left ventricular ejection fraction (LVEF) by echocardiography (p<0.01 vs pre-infusion), and the treatment effect (delta LVEF) was greater in the bFGF+MSCs group compared to saline (7.43±1.51% versus -10.07±2.94%; p<0.001). Morphologic analysis revealed an increased infarct wall thickness in the bFGF+MSCs group compared to all others (p<0.05), accompanied by increased vascular density and reduced apoptosis. Immunofluorescence demonstrated increased cell engraftment and enhanced vascular differentiation in the bFGF+MSCs group compared to MSCs alone (p<0.05). CONCLUSIONS: Retrograde coronary venous bFGF infusion augments engraftment and differentiation capacity of transplanted MSCs, recovering cardiac function and preventing adverse remodeling. This novel combined treatment and delivery method is a promising strategy for cardiac repair after ischemic injury.

Effect of beta-3 adrenoceptor stimulation on the levels of ApoA-I, PPARα, and PPARγ in apolipoprotein E-deficient mice.

The beta-3 adrenoceptor (ß3-AR) protects against the progression of atherosclerosis. However, the specific mechanism of this antiatherosclerotic effect is still not clear. Thus, the aim of this study was to understand the antiatherosclerotic effects of ß3-AR. Thirty-six male homozygous apolipoprotein E-deficient mice and wild-type C57BL/6J mice were randomized into 6 treatment groups: wild-type, atherosclerotic model, atorvastatin, low-dose ß3-AR agonist, high-dose ß3-AR agonist, and ß3-AR antagonist groups. The serum lipids, aortic-free cholesterol (FC), and cholesteryl ester (CE) concentrations were measured at the end of the treatments. The mRNA expression levels of liver apolipoprotein A-I (apoA-I), peroxisome proliferator-activated receptor-α (PPARα), and peroxisome proliferator-activated receptor-γ (PPARγ) were detected by quantitative real-time PCR. Protein expression levels of apoA1, PPARα, and PPARγ in the liver were determined by western blot analysis. Treatment with ß3-AR significantly increased the plasma levels of high-density lipoprotein cholesterol and apoA-I, whereas the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol decreased. The ß3-AR agonist treatment markedly decreased both the FC and the CE concentrations in the aorta compared with the atherosclerotic model mice. The ß3-AR agonist increased the mRNA and protein expression levels of apoA-I, PPARα, and PPARγ in the liver. This study demonstrates that long-term ß3-AR activation can regulate lipid metabolic disorders and reduces the aortic FC and the CE concentrations. These effects may be related to apoA-I, PPARα, and PPARγ.

Effect of nonylphenol on response of physiology and photosynthesis-related gene transcription of Chlorella vulgaris.

Nonylphenol (NP) is regarded as a kind of persistent organic pollutant which exists ubiquitously in the environment. The objective of this study was to evaluate the effects of NP on Chlorella vulgaris physiological indices and gene transcription. The results showed that NP stress inhibited algal growth in short-term bioassay. NP also decreased chlorophyll content, including chl a, chl b, and total chlorophyll. NP caused oxidant hurt by overproducing reactive oxygen species (ROS), which might destroy the overall membrane system to cause malondialdehyde content increase. NP inhibited photosynthesis-related gene transcription in C. vulgaris after 24 to 48 h exposure. The lowest transcript levels of psaB, psbA, and rbcL in C. vulgaris decreased to only 18.5%, 7%, and 4% of the control, respectively. Taken together, our results demonstrate that NP is toxic to fresh algae growth by affecting the photosynthesis-related genes transcription and overproducing ROS to disrupt cell structure in a short period.

[Effects of immune modulation therapy on cardiac function in aged patients with chronic heart failure].

OBJECTIVE: To investigate the effect of immune modulation therapy on cardiac function and lymphocyte subsets in aged patients with chronic heart failure (CHF). METHODS: CHF (NYHA classification: II-IV) patients older than 60 years were randomly divided into two groups: CHF intervention group received regular therapy and thymopetide (2 mg/day i.m. for 75 days, n = 48), CHF control group received regular therapy (n = 48), 45 healthy individuals older than 60 years served as normal control. Left ventricular ejection faction of (LVEF), inner diameter of left ventricular end-diastole (LVEDD), inner diameter of left ventricular end-systole (LVESD), lymphocyte subsets, plasma high sensitive C-reactive protein (hsCRP), plasma brain natrium peptide (BNP) and 6 minutes walking distance (6MWT) were measured at before therapy, after the first course (15 days) of treatment and after the third course of treatment (75 days). RESULTS: (1) Before therapy, the levels of BNP, hsCRP, CD8 T cells, LVEDD and LVESD were significantly higher and the levels of CD3, CD4, CD19 T cells, NK, CD4/CD8 ratio, LVEF and 6MWT were significantly lower in CHF patients compared to compared normal controls (all P < 0.05). These parameters were similar between CHF intervention group and CHF control group. (2) At 15 days, the levels of CD3, CD4, CD19 T cells and NK were significantly increased (P < 0.05 or P < 0.01) while the level of CD8, BNP and hsCRP were significantly decreased (P < 0.05 or P < 0.01) in CHF intervention group compared with CHF control group. (3) At 75 days, the levels of CD3, CD4, CD19 T cells, NK, CD4/CD8, LVEF and 6MWT were significantly increased (P < 0.05 or P < 0.01) while the levels of CD8, BNP, hsCRP and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were significantly decreased (P < 0.05 or P < 0.01) in CHF intervention group compared with CHF control group. CONCLUSION: Thymopetide, an immune modulating agent, might regulate the quantity and proportion of lymphocyte subsets and improve cardiac function in aged patients with CHF, indicating that immune modulation therapy might be a new treatment strategy for aged CHF patients.

Change of expression of renal alpha1-adrenergic receptor and angiotensin II receptor subtypes with aging in rats.

BACKGROUND AND AIMS: It has been considered that the functional decline of renal vasoconstriction during senescence is associated with an alteration in renal alpha1-adrenergic receptor (alpha1-AR) expression. While alterations in renal angiotensin II receptor (ATR) expression was considered to have an effect on renal structure and function, until now little information has been available concerning alpha1-AR and ATR expression variations over the entire aging continuum. The present study was undertaken to examine the expression levels of alpha1-AR and ATR subtypes in renal tissue during the spectrum running from young adulthood, to middle age, to the presenium, and to the senium. METHODS: Semiquantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western Blot were used to quantify the messenger RNA (mRNA) and protein levels of alpha1-AR and ATR subtypes in renal tissue in 3-month-old (young adult), 12-month-old (middle age), 18-month-old (presenium) and 24-month-old (senium) Wistar rats. RESULTS: alpha1A-AR expression decreased gradually with aging: it was decreased during middle age, the presenium and the senium, compared, respectively, with young adult values (p<0.01), and there was a significant decline both in the presenium with respect to middle age and in the senium with respect to the presenium. alpha1B-AR and alpha1D-AR expression were unmodified during senescence. AT1R expression was unaffected by aging during young adulthood and middle age, but exhibited a remarkable downregulation in the presenium and senium periods (p<0.01). AT2R expression was markedly increased in the senium (p<0.01). CONCLUSIONS: These results suggest that there are considerable variations in the expression levels of renal alpha1-AR and ATR subtypes during aging. alpha1A-AR expression downregulation may account for the reduced reactivity of renal alpha1-AR to vasoconstrictors and to renal function decline in the senium. Both the downregulation of AT1R and the upregulation of AT2R may be influential in maintaining normal physiological renal function during aging.

Age-dependent differential crosstalk between alpha(1)-adrenergic and angiotensin receptors.

BACKGROUND: Previous reports of crosstalk between alpha(1)- adrenergic receptors (alpha(1)-AR) and angiotensin receptors (ATR) have pointed to the existence of physiological regulation between the sympathetic nervous system and the renin-angiotensin system at the receptor level. This regulation may have an important role in the control of blood pressure and may be modified in different cardiovascular pathologies. Aging is considered to be an independent cardiovascular risk factor. Nevertheless, neither the variation in physiological action or interaction of signal transduction between these two receptors as a result of aging has been established. To clarify these aspects, the interaction between alpha(1)-AR and ATR was evaluated. METHODS: The inotropic response of alpha(1)-AR to agonists was assessed in the presence and absence of angiotensin II using the left atria of 3.5-, 12-, 18- and 24-month-old (young adult, middle aged, elderly and aged, respectively) male Wistar rats. In the four age groups of rat hearts, the activities of tyrosine kinase were measured when just the AT(1)R subtype was activated, or when both alpha(1)-AR and AT(1)R were activated. The activities of cytosolic phospholipase A(2) and the levels of cyclic GMP were investigated when just the AT(2)R subtype was activated, or when both alpha(1)-AR and AT(2)R were activated. RESULTS: No effect was found on the cumulative concentration-response curve for phenylephrine when AT(1)R was activated in 3.5- or 12-month-old rats. However, in 18- and 24-month-old rats, the maximum positive inotropic response and the negative logarithm of the effective 50% concentration increased markedly. No effect was found on the cumulative concentration response curve induced by phenylephrine when AT(2)R was activated. The activities of tyrosine kinase increased significantly in 3.5- and 12-month-old rats, but there was no difference in 18- and 24-month-old rats when alpha(1)-AR and AT(1)R were both activated compared with when just AT(1)R was activated. Cytosolic phospholipase A(2) activity and cyclic GMP levels decreased significantly when both alpha(1)-AR and AT(2)R were activated compared with when just AT(2)R was activated. CONCLUSIONS: In the isolated left atria of elderly and aged rats, the activation of AT(1)R enhanced the positive inotropic response induced by the activation of alpha(1)-AR. The activation of AT(2)R had no effect on the positive inotropic response induced by the activation of alpha(1)-AR. The action of alpha(1)-AR increased the signal transduction of AT(1)R in young-adult and middle-aged rat hearts but had no effect in elderly and aged hearts. The action of alpha(1)-AR had no effect on AT(2)R signal transduction.

Interaction of signal transduction between angiotensin AT1 and AT2 receptor subtypes in rat senescent heart.

BACKGROUND: Angiotensin II (Ang II) acting at angiotensin AT(1) receptor (AT(1)R) has well documented effects on cardiovascular structure such as the promotion of cardiovascular hypertrophy and fibrosis, which are believed to be opposed by angiotensin AT(2) receptor (AT(2)R) stimulation. The expressions of AT(1)R and AT(2)R are up-regulated in senescent hearts. The purpose of this study was to investigate the interaction of signal transduction between AT(1)R and AT(2)R, and to detect whether there is any difference in the interaction in rat hearts of different age. METHODS: In 3.5-, 12-, 18- and 24-month-old rats, the heart cell membrane activities of protein kinase C (PKC) and tyrosine kinase were measured when AT(1)R and AT(2)R were both activated by Ang II or just the AT(1)R was activated by Ang II and PD123319. The activities of cytosolic phospholipase A(2) (cPLA(2)) and the levels of cGMP were investigated when AT(1)R and AT(2)R were both activated by Ang II or just the AT(2)R was activated by Ang II and losartan. RESULTS: When AT(1)R and AT(2)R were both activated compared to when the AT(1)R was activated, the activities of PKC were not different in hearts from 3.5- and 12-month-old rats, but decreased significantly in 18- and 24-month-old rats; the activities of tyrosine kinase were not different in 3.5-month-old rats but decreased significantly in 12-, 18- and 24-month-old rats. The activities of cPLA(2) were all decreased significantly in rats of different age when AT(1)R and AT(2)R were both activated compared to when the AT(2)R was activated. Treatment with Ang II alone compared to Ang II and losartan decreased the levels of cGMP (fmol/mg) in rats of different age (102.7 +/- 12.7 versus 86.0 +/- 8.0 in 3.5-month-old rats, P < 0.05; 81.0 +/- 9.4 versus 70.0 +/- 6.3 in 12-month-old rats, P < 0.05; 69.8 +/- 5.6 versus 54.2 +/- 5.3 in 18-month-old rats, P < 0.01; 57.7 +/- 8.0 versus 39.0 +/- 3.0 in 24-month-old rats, P < 0.01). CONCLUSIONS: The activation of AT(1)R inhibited the signal transduction of AT(2)R during the aging variation, and the activation of AT(2)R inhibited the signal transduction of AT(1)R in rat heart of different age.