Cardioprotective Effects of HO-1-Loaded Collagen-Targeted Phase Change Nanoparticles on Cardiomyocytes Following Acute Myocardial Infarction

2021 ◽  
Vol 13 (9) ◽  
pp. 1685-1690
Author(s):  
Shangjun Liu ◽  
Wentao Duan ◽  
Xiangqun Zhou

Acute myocardial infarction (MI) is a major cause of death worldwide. This study utilized collagen-targeted phase change material (PCM) nanoparticles (NPs) to co-encapsulate HO-1 and explored the efficacy of composite PCM NPs on cardiomyocyte progression and development of MI. In this study, we enrolled 32 acute MI patients and 32 healthy participants, and ELISA assay was used to assess the content of creatine kinase isoenzyme (CK-MB). Mice with MI received tail vein administration of HO-1-loaded PCM NPs, followed by RT-qPCR detection of expressions of hypoxia-reoxygenation related genes (SpA, SpB, SpC, Occludin, KGF, and CK18). Patients with acute MI had a higher level of CK-MB. Treatment with HO-1-loaded collagen-targeted PCM NPs decreased expressions of SpA, SpB, SpC, Occludin, KGF, and CK18, facilitating repair of damaged tissues. Of note, NPs loaded with siRNA HO-1 up-regulated the expression of these genes. Collagen-targeted PCM NPs carrying HO-1 effectively promoted the repair of myocardial cells and relieved MI through down-regulation of hypoxia-reoxygenation related genes, which may enhance prevention and treatment for acute MI.

Author(s):  
Verena Summerer ◽  
Michael Arzt ◽  
Henrik Fox ◽  
Olaf Oldenburg ◽  
Florian Zeman ◽  
...  

Background In patients with acute myocardial infarction (MI), cardioprotective effects of obstructive sleep apnea are postulated on account of hypoxemic preconditioning. The aim of this single‐center substudy was to investigate a potential association between obstructive sleep apnea and the presence of coronary collaterals in patients with first‐time acute MI who have been enrolled in an ongoing, multicenter clinical trial. Methods and Results In TEAM‐ASV I (Treatment of Sleep Apnea Early After Myocardial Infarction With Adaptive Servo‐Ventilation Trial; NCT02093377) patients with first acute MI who received a coronary angiogram within 24 hours after onset of symptoms underwent polygraphy within the first 3 days. Coronary collaterals were classified visually by assigning a Cohen‐Rentrop Score (CRS) ranging between 0 (no collaterals) and 3. Of 94 analyzed patients, 14% had significant coronary collaterals with a CRS ≥2. Apnea‐Hypopnea Index (AHI) score was significantly higher in patients with CRS ≥2 compared with those with CRS <2 (31/hour [11–54] versus 13/hour [4–27]; P =0.032). A multivariable regression model revealed a significant association between obstructive AHI and CRS ≥2 that was independent of age, sex, body mass index, and culprit lesion left anterior descending artery (odds ratio [OR], 1.06; 95% CI, 1.01–1.12; P =0.023), but no significant association between coronary collaterals and central AHI (OR, 1.02; 95% CI, 0.97–1.08; P =0.443). Conclusions Patients with first‐time acute MI had more extensive coronary collateralization with an increased AHI or rather an increased obstructive AHI. This finding supports the hypothesis that obstructive sleep apnea exerts potential cardioprotective effects, in addition to its known deleterious effects, in patients with acute MI. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02093377.


1999 ◽  
Vol 82 (S 01) ◽  
pp. 68-72 ◽  
Author(s):  
Alessandro Sciahbasi ◽  
Eugenia De Marco ◽  
Attilio Maseri ◽  
Felicita Andreotti

SummaryPreinfarction angina and early reperfusion of the infarct-related artery are major determinants of reduced infarct-size in patients with acute myocardial infarction. The beneficial effects of preinfarction angina on infarct size have been attributed to the development of collateral vessels and/or to post-ischemic myocardial protection. However, recently, a relation has been found between prodromal angina, faster coronary recanalization, and smaller infarcts in patients treated with rt-PA: those with preinfarction angina showed earlier reperfusion (p = 0.006) and a 50% reduction of CKMB-estimated infarct-size (p = 0.009) compared to patients without preinfarction angina. This intriguing observation is consistent with a subsequent observation of higher coronary recanalization rates following thrombolysis in patients with prodromal preinfarction angina compared to patients without antecedent angina. Recent findings in dogs show an enhanced spontaneous lysis of plateletrich coronary thrombi with ischemic preconditioning, which is prevented by adenosine blockade, suggesting an antithrom-botic effect of ischemic metabolites. Understanding the mechanisms responsible for earlier and enhanced coronary recanalization in patients with preinfarction angina may open the way to new reperfusion strategies.A vast number of studies, globally involving ≈17,000 patients with acute myocardial infarction, have unequivocally shown that an infarction preceded by angina evolves into a smaller area of necrosis compared to an infarct not preceded by angina (Table 1) (1). So far, preinfarction angina has been thought to have cardioprotective effects mainly through two mechanisms: collateral perfusion of the infarctzone (2-4), and ischemic preconditioning of the myocardium (5-7). Here we discuss a further mechanism of protection represented by improved reperfusion of the infarct-related artery.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Jankowski ◽  
R Topor-Madry ◽  
M Gasior ◽  
U Ceglowska ◽  
Z Eysymontt ◽  
...  

Abstract Background Mortality following acute myocardial infarction (MI) remains high despite progress in pharmacotherapy and interventional treatment. In 2017 a nation-wide system of managed care for MI survivors comprising a continuum of acute treatment of MI, staged revascularization, cardiac rehabilitation, cardiac electrotherapy and cardiac ambulatory care within one year following MI was implemented in Poland. The managed care programme (MCP) includes also the quality of care assessment based on clinical measures (e.g. cardiovascular risk factors control) as well as on the rate of minor and major cardiovascular events. The goal of the analysis was to assess the overall mortality of MI survivors participating and not participating in the MCP. Methods The database of survivors of acute MI discharged from hospital from October 1, 2017 to December 31, 2018 was analyzed. Patients who died within 10 days after discharge were excluded from the analysis. The primary end-point was defined as death from any cause. Propensity-Score Matching (PSM) using nearest neighbor matching was used to form comparable groups of patients participating and not participating in the MCP. The Cox proportional hazard regression analysis was used to assess the relation between MCP and the overall mortality. Results MCP was implemented in the first stage in 48 hospitals spread around the country (about 34% of all hospitals treating acute MI patients in Poland). Out of 87739 analyzed patients (age: 68.1±11.9 years; 55581 men and 32158 women) 34064 were hospitalized in hospitals with MCP implemented. Altogether 10404 patients (11.9% of the whole cohort; 30.5% of those hospitalized in hospitals with MCP implemented) participated in MCP. They were matched with 10404 patients not participating in the MCP. During 324.8±140.5 days of follow-up 7413 patients died. One-year mortality was lower in patients participating in the MCP both when we analyzed the whole cohort (4.4% vs. 9.5%; p&lt;0.001) as well as when we limited the analysis to the PSM groups (4.4% vs. 6.5%; p&lt;0.001, figure 1). MCP was related to the overall mortality in univariate (HR 0.43 [0.39–0.48]) as well as in multivariate analysis (0.64 [0.57–0.71]) in the whole cohort as well as in the PSM cohort (HR 0.63 [0.56–0.72] and 0.64 [0.56–0.72] for the univariate and multivariate analysis respectively). When we limited the analysis to hospitals in which MCP was implemented one-year mortality was 4.3% vs. 6.3% (p&lt;0.001) whereas univariate HR was 0.51 (0.44–0.60) and multivariate HR 0.52 (0.44–0.61). Conclusion The implemented in Poland nation-wide system of managed care for MI survivors is related to improved survival. Therefore, the Ministry of Health plans to implement the programme in all cardiac centers in Poland. Funding Acknowledgement Type of funding source: None


Author(s):  
L. Derks ◽  
◽  
S. Houterman ◽  
G. S. C. Geuzebroek ◽  
P. van der Harst ◽  
...  

Abstract Background In multiple studies, the potential relationship between daylight saving time (DST) and the occurrence of acute myocardial infarction (MI) has been investigated, with mixed results. Using the Dutch Percutaneous Coronary Intervention (PCI) registry facilitated by the Netherlands Heart Registration, we investigated whether the transitions to and from DST interact with the incidence rate of PCI for acute MI. Methods We assessed changes in hospital admissions for patients with ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) undergoing PCI between 1 January 2015 and 31 December 2018. We compared the incidence rate of PCI procedures during the first 3 or 7 days after the transition with that during a control period (2 weeks before transition plus second week after transition). Incidence rate ratio (IRR) was calculated using Poisson regression. Potential gender differences were also investigated. Results A total of 80,970 PCI procedures for STEMI or NSTEMI were performed. No difference in incidence rate a week after the transition to DST in spring was observed for STEMI (IRR 0.95, 95% confidence interval (CI) 0.87–1.03) or NSTEMI (IRR 1.04, 95% CI 0.96–1.12). After the transition from DST in autumn, the IRR was also comparable with the control period (STEMI: 1.03, 95% CI 0.95–1.12, and NSTEMI: 0.98, 95% CI 0.91–1.06). Observing the first 3 days after each transition yielded similar results. Gender-specific results were comparable. Conclusion Based on data from a large, nationwide registry, there was no correlation between the transition to or from DST and a change in the incidence rate of PCI for acute MI.


2012 ◽  
Vol 58 (3) ◽  
pp. 559-567 ◽  
Author(s):  
Yvan Devaux ◽  
Mélanie Vausort ◽  
Emeline Goretti ◽  
Petr V Nazarov ◽  
Francisco Azuaje ◽  
...  

Abstract BACKGROUND Rapid and correct diagnosis of acute myocardial infarction (MI) has an important impact on patient treatment and prognosis. We compared the diagnostic performance of high-sensitivity cardiac troponin T (hs-cTnT) and cardiac enriched microRNAs (miRNAs) in patients with MI. METHODS Circulating concentrations of cardiac-enriched miR-208b and miR-499 were measured by quantitative PCR in a case-control study of 510 MI patients referred for primary mechanical reperfusion and 87 healthy controls. RESULTS miRNA-208b and miR-499 were highly increased in MI patients (&gt;105-fold, P &lt; 0.001) and nearly undetectable in healthy controls. Patients with ST-elevation MI (n= 397) had higher miRNA concentrations than patients with non–ST-elevation MI (n = 113) (P &lt; 0.001). Both miRNAs correlated with peak concentrations of creatine kinase and cTnT (P &lt; 10−9). miRNAs and hs-cTnT were already detectable in the plasma 1 h after onset of chest pain. In patients who presented &lt;3 h after onset of pain, miR-499 was positive in 93% of patients and hs-cTnT in 88% of patients (P= 0.78). Overall, miR-499 and hs-cTnT provided comparable diagnostic value with areas under the ROC curves of 0.97. The reclassification index of miR-499 to a clinical model including several risk factors and hs-cTnT was not significant (P = 0.15). CONCLUSION Circulating miRNAs are powerful markers of acute MI. Their usefulness in the establishment of a rapid and accurate diagnosis of acute MI remains to be determined in unselected populations of patients with acute chest pain.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Alexander E Merkler ◽  
Gino Gialdini ◽  
Santosh Murthy ◽  
Shadi Yaghi ◽  
Babak Navi ◽  
...  

Background: Acute myocardial infarction (MI) has long been reported as a risk factor for ischemic stroke, but the magnitude and duration of risk remains uncertain. Methods: We performed a crossover-cohort study using inpatient and outpatient claims data from a nationally representative 5% sample of Medicare beneficiaries from 2008 through 2014. We identified all patients ≥66 years of age with a first-recorded hospitalization for acute MI. The primary outcome was ischemic stroke. All predictors and outcomes were defined using previously validated ICD-9-CM codes. To exclude stroke that may have been due to percutaneous coronary intervention, we included only cases of ischemic stroke that occurred after discharge from the MI hospitalization. We compared the risk of ischemic stroke in successive 4-week periods during the 12 weeks after MI versus the corresponding 4-week periods 1 year later. To avoid immortal time bias, we limited our cohort to patients who remained alive and insured throughout the 15 month study period. Odds ratios (OR) and absolute risk differences were calculated using the Mantel-Haenszel estimator for matched data. Results: We identified 22,798 patients with an acute MI in whom the mean age was 77.4 (±7.9) years and 50.3% were women. In the 12 weeks after discharge, 216 patients (0.95%) developed a stroke, as compared to 21 (0.09%) patients in the corresponding 12-week period 1 year later. The absolute increase in stroke risk was 0.45% (95% confidence interval [CI], 0.36-0.55%) in the first 4 weeks after acute MI compared to the 4-week time period 1 year later, corresponding to an OR of 18.2 (95% CI, 8.1-50.6). The absolute risk increase was 0.24% (95% CI, 0.16-0.31%) during weeks 5-8 (OR, 8.7; 95% CI, 4.0-22.6) and 0.17% (95% CI, 0.10-0.23%) during weeks 9-12 (OR, 5.8; 95% CI, 2.7-14.1). Conclusions: Acute MI is associated with a substantially elevated short-term risk of ischemic stroke. This risk was independent of periprocedural stroke risk in the setting of coronary reperfusion therapies.


2017 ◽  
Vol 118 (4) ◽  
pp. 303-311 ◽  
Author(s):  
Dongqing Wang ◽  
Hannia Campos ◽  
Ana Baylin

AbstractThe adverse effect of red meat consumption on the risk for CVD is a major population health concern, especially in developing Hispanic/Latino countries in which there are clear trends towards increased consumption. This population-based case–control study examined the associations between total, processed and unprocessed red meat intakes and non-fatal acute myocardial infarction (MI) in Costa Rica. The study included 2131 survivors of a first non-fatal acute MI and 2131 controls individually matched by age, sex and area of residence. Dietary intake was assessed with a FFQ. OR were estimated by using conditional logistic regression. Higher intakes of total and processed red meat were associated with increased odds of acute MI. The OR were 1·31 (95 % CI 1·04, 1·65) and 1·29 (95 % CI 1·01, 1·65) for the highest quintiles of total red meat (median: 110·8 g or 1 serving/d) and processed red meat intake (median: 36·1 g or 5 servings/week), respectively. There were increasing trends in the odds of acute MI with higher total (Ptrend=0·01) and processed (Ptrend=0·02) red meat intakes. Unprocessed red meat intake was not associated with increased odds of acute MI. Substitutions of 50 g of alternative foods (fish, milk, chicken without skin and chicken without fat) for 50 g of total, processed and unprocessed red meat were associated with lower odds of acute MI. The positive association between red meat intake and acute MI in Costa Rica highlights the importance of reducing red meat consumption in middle-income Hispanic/Latino populations.


2018 ◽  
Vol 20 (4) ◽  
pp. 396-406 ◽  
Author(s):  
Toshiyuki Kimura ◽  
Véronique L Roger ◽  
Nozomi Watanabe ◽  
Sergio Barros-Gomes ◽  
Yan Topilsky ◽  
...  

Abstract Aims Mechanisms of chronic ischaemic mitral regurgitation (IMR) are well-characterized by apically tethered leaflet caused by papillary muscles (PMs) displacement and adynamic mitral apparatus. We investigated the unique geometry and dynamics of the mitral apparatus in first acute myocardial infarction (MI) by using quantified 3D echocardiography. Methods and results We prospectively performed 3D echocardiography 2.3 ± 1.8 days after first MI, in 174 matched patients with (n = 87) and without IMR (n = 87). 3D echocardiography of left ventricular (LV) volumes and of mitral apparatus dynamics throughout cardiac cycle was quantified. Similar mitral quantification was obtained at chronic post-MI stage (n = 44). Mechanistically, acute IMR was associated with larger and flatter annulus (area 9.29 ± 1.74 cm2 vs. 8.57 ± 1.94 cm2, P = 0.002, saddle shape 12.7 ± 4.5% vs. 15.0 ± 4.6%, P = 0.001), and larger tenting (length 6.36 ± 1.78 mm vs. 5.60 ± 1.55 mm, P = 0.003) but vs. chronic MI, mitral apparatus displayed smaller alterations (all P < 0.01) and annular size, PM movement remained dynamic (all P < 0.01). Specific to acute IMR, without PM apical displacement (P > 0.70), greater separation (21.7 ± 4.9 mm vs. 20.0 ± 3.4 mm, P = 0.01), and widest angulation of PM (38.4 ± 6.2° for moderate vs. 33.5 ± 7.3° for mild vs. 31.4 ± 6.3° for no-IMR, P = 0.0009) wider vs. chronic MI (P < 0.01). Conclusions 3D echocardiography of patients with first MI provides insights into unique 4D dynamics of the mitral apparatus in acute IMR. Mitral apparatus remained dynamic in acute MI and distinct IMR mechanism in acute MI is not PM displacement seen in chronic IMR but separation and excess angulation of PM deforming the mitral valve, probably because of sudden-onset regional wall motion abnormality without apparent global LV remodelling. This specific mechanism should be considered in novel therapeutic strategies for IMR complicating acute MI.


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