Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

Comparison of direct stenting with conventional strategy on myocardial impairments in ST-segment elevation myocardial infarction: a cardiac magnetic resonance imaging study.

Direct stenting (DS) without pre-dilatation of the culprit lesion might improve myocardial perfusion and prognosis in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI); however, some studies report conflicting results. We investigated whether DS provides incremental myocardial benefits over conventional stenting (CS) in STEMI patients based on cardiac magnetic resonance imaging (CMR) measures. Reperfused patients who underwent CMR examinations within 1 week of STEMI onset were selected from a multicenter CMR registry of STEMI (NCT: 03768453). Patients were stratified into either a DS or CS group. Each group comprised 137 patients after 1:1 propensity score matching. Major adverse events (MACEs), including death, myocardial re-infarction, re-admission for heart failure, and stroke were noted during a median period of 44 months (interquartile range 32-58 months). DS was associated with larger (p = 0.007) and shorter (p = 0.005) stent sizes than CS. DS and CS achieved comparable angiographic TIMI-3 flow grades (p = 0.86) and myocardial blush grades (p = 0.70). There were no group differences regarding the incidence of CMR manifestations of microvascular dysfunction, including microvascular obstruction (MVO) (p = 0.89) and intramyocardial hemorrhage (p = 0.47), the extent of MVO (p = 0.21), infarction size (p = 0.83), or left ventricular ejection fraction (p = 0.57). Kaplan-Meier analysis revealed similar risks of MACEs (log rank p = 0.909), which occurred in 23.4% of DS and 26.3% of CS patients (p = 0.576). DS did not show any incremental benefits over CS on myocardial impairments as evaluated using CMR.Clinical Trial Registration: Clinicaltrials.gov, NCT: 03768453.

LncRNA-RP11-714G18.1 suppresses vascular cell migration via directly targeting LRP2BP.

Atherosclerotic cardiovascular disease is considered as the leading cause of mortality and morbidity worldwide. Accumulating evidence supports an important role for long noncoding RNA (lncRNA) in the pathogenesis of atherosclerosis. Nevertheless, the role of lncRNA in atherosclerosis-associated vascular dysfunction and the underlying mechanism remain elusive. Here, using microarray analysis, we identified a novel lncRNA RP11-714G18.1 with significant reduced expression in human advanced atherosclerotic plaque tissues. We demonstrated in both human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) that RP11-714G18.1 impaired cell migration, reduced the adhesion of ECs to monocytes, suppressed the neoangiogenesis, decreased apoptosis of VSMCs and promoted nitric oxide production. Mechanistically, RP11-714G18.1 could directly bind to its nearby gene LRP2BP and increased the expression of LRP2BP. Moreover, we showed that RP11-714G18.1 impaired cell migration through LRP2BP-mediated downregulation of matrix metalloproteinase (MMP)1 in both ECs and VSMCs. In atherosclerotic patients, the serum levels of LRP2BP were positively correlated with high-density lipoprotein cholesterol, but negatively correlated with cardiac troponin I. Our study suggests that RP11-714G18.1 may play an athero-protective role by inhibiting vascular cell migration via RP11-714G18.1/LRP2BP/MMP1 signaling pathway, and targeting the pathway may provide new therapeutic approaches for atherosclerosis.

[Clinical outcomes of intravascular ultrasound in guiding the treatment of non-left main intermediate coronary lesions for patients with acute coronary syndrome].

OBJECTIVE: To evaluate the long-term clinical outcomes of intravascular ultrasound(IVUS) in guiding the treatment of non-left main intermediate coronary lesions for patients of acute coronary syndrome (ACS). METHODS: A total of 25 patients with intermediate coronary lesions(stenosis of 40%-70%) confirmed by coronary angiography were performed with IVUS. When MLA≥4 mm2, we deferred the PCI treatment and performed optimal medical treatment (OMT). The patient were followed up for 12 month. The primary outcome was target vessel revascularization (TVR) and secondary outcome was major adverse cardiac events (MACEs). RESULTS: A total of 25 lesions of 25 patients were examined by IVUS. 19(76%) lesions were attenuated plaque, 4(16%)were echo-lucent plaque, 2(8%) were calcified plaque. Most of the plaque (18/25, 72%) were eccentric. Positive remodeling was found in 20(80%) lesions and negative remodeling in 5(20%) lesions with meanremodeling index of 1.17=0.15. Thrombus was found in 1 case, accounting for 4%. The diameter stenosis, area stenosis, minimal lumen area and the reference diameter mea-sured by IVUS were larger than those measured by quantitative coronary angiography (all P<0.05). One patient with non-ST segment elevated myocardiac infarction was performed revascularization because MI attacked again, and 2 patients with Unstable angina were treated with OMT but they were still rehospitalization because of angina occurred repeatedly. The incidence of TVR was 4.00%, so as 16.00% of MACE. CONCLUSION: IVUS can be used to guide the treatment of non-left main intermediate coronary lesions for patients of acute coronary syndrome.

Long Noncoding RNA HOXC-AS1 Suppresses Ox-LDL-Induced Cholesterol Accumulation Through Promoting HOXC6 Expression in THP-1 Macrophages.

Atherosclerosis is a common pathological basis of cardiovascular disease, which remains the leading cause of mortality. Long noncoding RNAs (lncRNAs) are newly studied non-protein-coding RNAs involved in gene regulation, but how lncRNAs exert regulatory effect on atherosclerosis remains unclear. In this study, we found that lncRNA HOXC cluster antisense RNA 1 (HOXC-AS1) and homeobox C6 (HOXC6) were downregulated in carotid atherosclerosis by performing microarray analysis. The results were verified in atherosclerotic plaques and normal arterial intima tissues by quantitative reverse transcription PCR and western blot analysis. Lentivirus-mediated overexpression of HOXC-AS1 induced HOXC6 expression at mRNA and protein levels in THP-1 macrophages. Besides, oxidized low-density lipoprotein (Ox-LDL) decreased expression of HOXC-AS1 and HOXC6 in a time-dependent manner. Induction of cholesterol accumulation by Ox-LDL could be partly suppressed by overexpression of HOXC-AS1.

VNN1 promotes atherosclerosis progression in apoE-/- mice fed a high-fat/high-cholesterol diet.

Accumulated evidence shows that vanin-1 (VNN1) plays a key part in glucose metabolism. We explored the effect of VNN1 on cholesterol metabolism, inflammation, apoptosis in vitro, and progression of atherosclerotic plaques in apoE(-/-) mice. Oxidized LDL (Ox-LDL) significantly induced VNN1 expression through an ERK1/2/cyclooxygenase-2/PPARα signaling pathway. VNN1 significantly increased cellular cholesterol content and decreased apoAI and HDL-cholesterol (HDL-C)-mediated efflux by 25.16% and 23.13%, respectively, in THP-1 macrophage-derived foam cells (P < 0.05). In addition, VNN1 attenuated Ox-LDL-induced apoptosis through upregulation of expression of p53 by 59.15% and downregulation of expression of B-cell lymphoma-2 127.13% in THP-1 macrophage (P < 0.05). In vivo, apoE(-/-) mice were divided randomly into two groups and transduced with lentivirus (LV)-Mock or LV-VNN1 for 12 weeks. VNN1-treated mice showed increased liver lipid content and plasma levels of TG (124.48%), LDL-cholesterol (119.64%), TNF-α (148.74%), interleukin (IL)-1ß (131.81%), and IL-6 (156.51%), whereas plasma levels of HDL-C (25.75%) were decreased significantly (P < 0.05). Consistent with these data, development of atherosclerotic lesions was increased significantly upon infection of apoE(-/-) mice with LV-VNN1. These observations suggest that VNN1 may be a promising therapeutic candidate against atherosclerosis.

Dihydrocapsaicin suppresses proinflammatory cytokines expression by enhancing nuclear factor IA in a NF-κB-dependent manner.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease and represents the leading cause of morbidity and mortality throughout the world. Accumulating evidences have showed that Dihydrocapsaicin (DHC) has been found to exert multiple pharmacological and physiological effects. Nevertheless, the effects and possible mechanism of DHC on proinflammatory response remain largely unexplained. METHODS AND RESULTS: We found that DHC markedly upregulated NFIA and suppressed NF-κB expression in THP-1 macrophages. Up-regulation of proinflammatory cytokines induced by LPS including TNF-α, IL-1ß and IL-6 were markedly suppressed by DHC treatment. We also observed that protein level of NFIA was significantly increased while NF-κB and proinflammatory cytokines were decreased by DHC treatment in apoE(-/-) mice. Lentivirus-mediated overexpression of NFIA suppressed NF-κB and proinflammatory cytokines expression both in THP-1 macrophages and plaque tissues of apoE-/- mice. Moreover, treatment with lentivirus-mediated overexpression of NFIA made the down-regulation of DHC on NF-κB and proinflammatory cytokines expression notably accentuated in THP-1 macrophages and apoE(-/-) mice. In addition, treatment with siRNA targeting NF-κB accentuated the suppression of proinflammatory cytokines by lentivirus-mediated overexpression of NFIA. CONCLUSION: These observations demonstrated that DHC can significantly decrease proinflammatory cytokines through enhancing NFIA and inhibiting NF-κB expression and thus DHC may be a promising candidate as an anti-inflammatory drug for atherosclerosis as well as other disorders.

MicroRNA-125b-5p attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production by targeting inhibiting LACTB in THP-1 macrophages.

BACKGROUND: Increasing evidence has shown that gene beta-lactamases (LACTB) has effect on obesity. Recent studies demonstrate that miR-125b-5p is a potential small molecular target to prevent atherosclerosis obliterans which may be inflammation-associated. However, the mechanism underlying miR-125b-5p on arteriosclerosis development, the association between miR-125b-5p and LACTB is still unknown. METHODS AND RESULTS: In this study, we found that miR-125b-5p was down-regulated while LACTB was up-regulated in atherosclerotic plaques. Our results showed that LACTB was a potential target of miR-125b-5p based on bioinformatics analyses and dual-luciferase reporter assays. Moreover, miR-125b-5p directly inhibited LACTB protein and mRNA expression by targeting LACTB 3'UTR. Meanwhile, the expression of monocyte chemotactic protein-1 (MCP-1) was decreased by miR-125b-5p mimics treatment in THP-1 macrophages. We also demonstrated that the level of MCP-1 was markedly increased when transfected with LACTB. In addition, the upregulation of MCP-1 expression through miR-125b-5p inhibitors was attenuate by siRNA-LACTB treatment in LPS-stimulated THP-1 macrophages. CONCLUSIONS: MiR-125b-5p attenuates the secretion of MCP-1 by directly targeting inhibiting LACTB in LPS-stimulated THP-1 macrophages.

[Evaluation of two arterial closure devices, Angioseal and Perclose, in coronary catheter interventions].

OBJECTIVE: To assess the efficacy and safety of two arterial closure devices, Angioseal and Perclose, in patients undergoing coronary angiography and invasive interventions. METHODS: From January 2001 to April 2011, 997 inpatients underwent coronary angiography and interventions with arterial closure using Perclose (486 cases) or Angioseal (511 cases). The time to ambulation and hemostasis, major vascular complications and deployment success rate with the two devices were compared. RESULTS: The time to hemostasis was significantly shorter in Angioseal group than in Perclose group (3∓0.9 min vs 10.8∓4.8 min, P<0.001), but the time to ambulation was comparable between the two groups (6.4∓1.2 h vs 6.3∓0.7 h, P>0.05). The incidences of vascular complications showed no significant differences between the two groups (4.5% vs 3.7%, P>0.05), and none of the cases in either group developed femoral artery thrombosis or low limb embolism following the procedures. The deployment success rate was comparable between the two groups (97.8% vss 98.6%, P>0.05), and deployment failure was associated mainly with mishandling and design defect of the devices. CONCLUSIONS: Angioseal and Perclose are both effective and safe for arterial closure with reduced hemostasis and ambulation time and low incidences of vascular complications. Angioseal appears to have better performance than Perclose in shortening the hemostasis time and is easier to handle.

[Plasma matrix metalloproteinases-2 and -9 levels are elevated in patients with acute coronary syndrome and coronary chronic total occlusion].

OBJECTIVE: To investigate the changes in plasma matrix metalloproteinases-2 and -9 (MMP2 and MMP9, respectively) levels in patients with different types of coronary heart diseases (CHD), and assess the value of MMP2/MMP9 detection in predicting acute coronary syndrome (ACS). METHODS: According to the findings by coronary angiography and the clinical manifestations, 118 patients were divided in ACS group including 30 patients with unstable angina pectoris (UAP) and 19 with acute myocardial infarction (AMI) and non-ACS group including 23 patients with stable angina pectoris (SAP) and 21 with chronic total occlusion (CTO) of the coronary artery. Twenty-five individuals with normal coronary artery (NCA) served as the control group. Plasma levels of MMP9 and MMP2 were determined in these subjects using enzyme-linked immunosorbent assay (ELISA). RESULTS: Both the ACS and non-ACS groups showed significantly higher MMP9 and MMP2 levels than the NCA group (P<0.05), and MMP2 and MMP9 levels were significantly higher in ACS group than in non-ACS group (P<0.05). Compared with the NCA group, the UAP, AMI and CTO subgroups showed obvious increases in plasma MMP2 and MMP9 levels (P<0.01). Significantly increased MMP9, but not MMP2 level was noted in AMI subgroup in comparison with SAP (P<0.01) and UAP subgroups (P<0.05); both MMP2 and MMP9 levels were elevated in CTO subgroup in comparison with those in SAP (P<0.001), UAP (P<0.01), and AMI subgroups (P<0.05). CONCLUSION: Increased MMP2 and MMP9 levels in patients with CHD suggest the instability of the atherosclerotic plaque in correlation to the severity of ACS, and may serve as good indicators for the prediction of ACS and diagnosis of CTO of the coronary artery.

[Targeted delivery of bone marrow mesenchymal stem cells by ultrasound-mediated microbubble destruction].

OBJECTIVE: To investigate the feasibility of bone marrow mesenchymal stem cell (MSC) transplantation with ultrasound-targeted microbubble destruction. METHODS: Twenty-one Wistar rats were divided into MSCs-iv group (MSCs-iv), ultrasound+MSCs-iv group (US+MSCs-iv), ultrasound+microbubble+MSCs-iv group (US+MB+MSCs-iv) with intravenous MSC transfer, ultrasound and microbubble treatment as indicated. The skeletal muscles were obtained from the rats for microscopic examination with HE staining. The hindlimb gracilis and semimembranosus muscles were sampled 7 days after MSC transplantation, and the transplanted MSCs were detected by immunohistochemistry. The vital organs were collected from rats in US+MB+MSCs-iv group for immunohistochemistry. RESULTS: In US+MB+MSCs-iv group, HE staining demonstrated the presence of red blood cell leakage into the tissue space in the gracilis and semimembranosus muscles, and immunohistochemistry identified large numbers of transplanted MSCs in the the gracilis and semimembranosus muscles and the spleen, whereas no labeled cells were detected in the skeletal muscles in other groups. CONCLUSION: Ultrasound-targeted microbubble destruction provides a useful means for enhancing the efficiency of stem cell transplantation.

[Evaluation of left ventricular diastolic function using velocity vector imaging and quantitative tissue velocity imaging].

OBJECTIVE: To validate the efficacy of velocity vector imaging (VVI) and quantitative tissue velocity imaging (QTVI) for evaluating left ventricular diastolic function. METHODS: Fifty-one patients underwent left heart catheterization were included in this study. Mean of peak early diastolic velocity (Em), EF and the ratio of early (E) to late (A) mitral valve flow velocity (E/A) were measured by echocardiography and the ratio of E to Em (E/Em) was calculated. Left ventricular end diastolic pressure (LVEDP) was measured during catheterization examination. RESULTS: E/Em derived from VVI or QTVI was significantly correlated with LVEDP (r = 0.808, P < 0.01 and r = 0.692, P < 0.01, respectively) and the correlation coefficient between VVI and LVEDP was significantly higher than that between QTVI and LVEDP (Z = 2.246, P = 0.025). Em derived from VVI and QTVI also negatively correlated with LVEDP (r = -0.740, P < 0.01 and r = -0.567, P < 0.01) and the correlation coefficient between VVI and LVEDP was significantly higher than that between QTVI and LVEDP (Z = 2.595, P = 0.009). However, there was no correlation between E/A and LVEDP (r = 0.117, P = 0.415). CONCLUSION: E/Em and Em derived from VVI and QTVI are valuable parameters for evaluating LV diastolic function.

[Ultrasound-mediated microbubble destruction increases capillary permeability in rat skeletal muscles].

OBJECTIVE: To investigate the effects of ultrasound mediated microbubble destruction on capillary permeability in rat skeletal muscles. METHODS: Eighteen SD rats were randomized into 3 groups, namely the Evans blue (EB) group, EB+ultrasound (E+U) group and EB+microbubble+ultrasound (U+E+M) group with corresponding treatments, using EB injected into the carotid artery as the indicator for capillary permeability. The microbubbles were injected through the carotid artery with fixed ultrasound parameters. The spillover of EB was estimated under fluorescence microscope according to the visual staining scores. The contents of EB in the skeletal muscles were calculated according to the standard curve and spectrophotometry. RESULTS: EB spillover was observed around the capillaries in E+U+M group, which had a significantly higher visual score than EB group and E+U group (0 and 0-1, respectively, P<0.05). The EB content was 51.57-/+3.89 microg/g in E+U+M group, also significantly higher than those in EB group (28.99-/+4.67 microg/g) and E+U group (30.99-/+4.11 microg/g) (P<0.05). CONCLUSION: Exposure to both ultrasound and microbubble contrast agents results in increased capillary permeability of rat skeletal muscles, which might be an important mechanisms for gene delivery enhancement by ultrasound contrast agents.

[Effect of microbubble cavitation on microcirculation of rat skeletal muscle].

OBJECTIVE: To investigate the effect of therapeutic ultrasound-induced microbubble destruction on the microcirculation of rat skeletal muscle. METHODS: Thirty SD rats were randomized into 5 groups (n=6), namely normal saline, microbubble, ultrasound, high-energy ultrasound microbubble and low-energy ultrasound microbubble groups. Before and after the treatments, the diameter and blood flow velocity in the microvessels in the skeletal muscle were measured, and the structural changes of the injured microvessels observed by electron microscopy. RESULTS: Microbubble cavitation did not produce significant effect on the mean arterial pressure and diameter of microvessels in rat skeletal muscle (P>0.05), but the blood flow velocity was obviously lowered and blood flow volume reduced in the microvessels. The reduction of the flow velocity and blood flow volume and their subsequent recovery were associated with ultrasound energy, and in the low ultrasound energy group, the flow velocity and blood flow volume in the of venules recovered obviously after about 15 min, which, however, took approximately 1 h for the arterioles. In contrast, recovery of the flow velocity and blood flow volume in the microvessels took more than 2 h in the high ultrasound energy group. Cavitation resulted in endothelium cell rupture, widening of the endothelial interspace and entry of the red blood cells into the extravascular tissues as revealed by electron microscopy, but no rupture of the lining endothelium was observed 2 h after the treatment. CONCLUSIONS: Endothelium cell rupture induced by microbubble cavitation may affect the local microcirculation, and lower ultrasound energy exposure is associated with milder endothelial injury and more rapid recovery.

[Construction of eukaryotic expression vectors of two mutants of hypoxia-inducible factor-1 and their expressions in human microvascular endothelial cells].

OBJECTIVE: To construct eukaryotic expression vectors of two mutants of hypoxia-inducible factor-1 (HIF-1alpha) and study their expressions in human microvascular endothelial cells (HMVECs). METHODS: Site-directed mutagenesis was performed to induce the mutation of the codons for the residue Pro564 (ccc) in HIF-1alpha into gcc (Ala) in pcDNA3.1(+)-HIF-1alphato obtain single-site-mutated vector pcDNA3.1(+)-HIF-1alpha-564Ala, which was then subjected to a second site-directed mutagenesis to convert the codons for Asn803 into that of Ala (gct) to acquire double-site-mutated pcDNA3.1(+)-HIF-1alpha-564Ala-803Ala. After lipofectin-mediated transient transformation of HMVECs with the 3 recombinant plasmids including the two plasmids containing the mutations and the one without mutation, respectively, the expression levels of HIF-1alpha mRNA and protein were determined using RT-PCR, immunofluorescent staining and Western blotting. RESULTS: DNA sequence analysis demonstrated success of the two-step mutagenesis and the two plasmids of pcDNA3.1+-HIF-1alpha-564Ala and pcDNA3.1(+)-HIF-1alpha-564Ala- 803Ala were obtained, both of which could produce HIF-1alpha protein resistant to oxidation degradation in HMVECs as compared with the non-mutated one. CONCLUSION: The recombinant plasmids pcDNA3.1(+)-HIF-1alpha-564Ala and pcDNA3.1(+)-HIF-1alpha- 564Ala-803Ala have been successfully constructed with efficient expressions in HMVECs.

[Targeted adhesion of platelet receptor-specific microbubble agent to thrombus in vitro].

OBJECTIVE: To examine the thrombus-targeting effect of platelet receptor-specific lipid microbubbles. METHODS: The targeted microbubbles were prepared by coupling Arg-Gly-Asp-Ser (RGDS) with the lipid microbubbles, which were added to the microthrombus generated by platelet aggregation. The effects of the targeted microbubbles on the ultrasonic signal was observed in an artificial thrombus model. RESULTS: The targeted microbubbles were adhesive to the microthrombus, while the non-targeted microbubbles did not possess this property. The ultrasonic signal of the thrombus border was enhanced significantly after the addition of the targeted microbubbles. CONCLUSIONS: Platelet receptor-specific microbubbles possess significant adhesive property to the thrombus and can improve signal-to-noise ratio of the thrombus, suggesting the potential value of the targeted microbubbles for clinical application in the diagnosis and treatment of thrombus.

[Ultrasound microbubbles promote thrombolysis of rabbit femoral artery thrombus].

OBJECTIVE: To evaluate the efficacy of intravenous ultrasound microbubbles for thrombolysis of arterial thrombus without using thrombolytic drugs. METHODS: Twelve rabbit models of acute bilateral femoral artery thrombosis were established and 6 of them received transcutaneous ultrasound and intravenous albumin microbubble treatment for thrombosis on one side while only microbubble treatment for the other side. The other 6 rabbits received ultrasound treatment on one side but no treatment on the other to serve as the control group. RESULTS: None of the 6 arteries treated with microbubbles alone and only 2 arteries treated with ultrasound alone in the 6 control rabbits were recanalized. All the 6 femoral arteries treated with microbubbles together with ultrasound were recanalized (P=0.014), with significantly shorter patent time and smaller residual thrombus cross-sectional area than those of the arteries with only ultrasound treatment (P=0.004 and P=0.003, respectively). CONCLUSION: Treatment with intravenous microbubbles assisted by transcutaneous ultrasound effectively promotes arterial thrombolysis in vivo, and this technique can be of significance in clinical treatment of acute thrombotic occlusions.

[Conditions of contrast ultrasound that affect the proliferation of rat smooth muscle cells].

OBJECTIVE: To investigate the effect of an echo-contrast agent on the proliferation of rat smooth muscle cells under different ultrasound conditions. METHODS: The vascular smooth muscle cells of rats were cultured with echo-contrast agent in 96-well plates, followed by exposure to ultrasound of different conditions. Trypan blue staining was performed 48 h later, and the proliferation of the cells observed by MTT assay. RESULTS: No cytotoxicity was found by trypan blue staining when the mechanical index of ultrasound was below 0.75. Compared with the control cells, the proliferation of the smooth muscle cells was decreased following the exposure as the mechanical index of ultrasound increased. The most obvious inhibition of cell proliferation was resulted when the microbubble concentration was 20% for a 60-second exposure. CONCLUSIONS: The inhibition of the vascular smooth muscle cell proliferation by echo-contrast agent destruction is correlated with the mechanical index of the ultrasound, concentration of the echo-contrast agent, and exposure time of ultrasound.