Cardiac Healing Research Articles

Advanced Nanosystems for Clinical Translation

Advanced Nanosystems for Clinical Translation

Repurposing From Oncology to Cardiology: Low-Dose 5-Azacytidine Attenuates Pathological Cardiac Remodeling in Response to Pressure Overload Injury

Recent evidence suggests that transcriptional reprogramming is involved in the pathogenesis of cardiac remodeling (cardiomyocyte hypertrophy and fibrosis) and the development of heart failure. 5-Azacytidine (5aza), an inhibitor of DNA methylation approved for hematological malignancies, has previously demonstrated beneficial effects on cardiac remodeling in hypertension. The aim of our work was to investigate whether pressure overload is associated with alterations in DNA methylation and if intervention with low-dose 5aza can attenuate the associated pathological changes. C57Bl6/J mice underwent surgical constriction of the aortic arch for 8 weeks. Mice began treatment 4 weeks post-surgery with either vehicle or 5aza (5 mg/kg). Cardiac structure and function was examined in vivo using echocardiography followed by post mortem histological assessment of hypertrophy and fibrosis. Global DNA methylation was examined by immunostaining for 5-methylcytosine (5MeC) and assessment of DNA methyltransferase expression. The results highlighted that pressure overload-induced pathological cardiac remodeling is associated with increased DNA methylation (elevated cardiac 5MeC positivity and Dnmt1 expression). Administration of 5aza attenuated pathological remodeling and diastolic dysfunction. These beneficial changes were mirrored by a treatment-related reduction in global 5MeC levels and expression of Dnmt1 and Dnmt3B in the heart. DNA methylation plays an important role in the pathogenesis of pressure overload-induced cardiac remodeling. Therapeutic intervention with 5aza, at a dose 5 times lower than clinically given for oncology treatment, attenuated myocardial hypertrophy and fibrosis. Our work supports the rationale for its potential use in cardiac pathologies associated with aberrant cardiac wound healing.

Abstract 17388: Loss of Bone Morphogenetic Protein 9 (BMP9) Limits Survival and Paradoxically Increases Collagen Abundance, but Limits Collagen Cross-Linking in a Murine Model of Acute Myocardial Infarction

Myocardial infarction (MI) is a major cause of heart failure (HF). HF is associated with adverse cardiac remodeling that is primarily driven by Transforming growth factor beta (TGFb1) mediated fibrosis and myocyte hypertrophy. We previously reported that loss of bone morphogenetic protein 9 (BMP9) promotes cardiac fibrosis in pressure-overload induced HF. No studies have explored a role for BMP9 in post MI cardiac remodeling. We hypothesize that loss of BMP9 may promote cardiac healing by stabilizing LV scar formation. To test this hypothesis, we subjected whole body BMP9 knockout (-/-) mice to left coronary artery ligation for two weeks followed by PV loop analysis and studied indices of cardiac remodeling. Compared to wild type (WT) controls BMP9-/- mice had significantly lower survival (83% vs 61%, p<0.001, respectively) with a higher rate of cardiac rupture(15% vs 90%). Compared to WT controls, surviving BMP9-/- mice had higher LVEDP, reduced LV dP/dt, and higher lung weight. Compared to WT mice, BMP9-/- mice had significantly higher levels of Type I collagen (2 fold p<0.05). Compared to WT mice, BMP9-/- mice had increased matrix metalloproteinases (MMP)-2 and MMP-9 (2.5 fold p<0.05) activity levels in the LV. Treatment of cultured primary human cardiac fibroblasts with recombinant BMP9 attenuated TGFb1-mediated Type I collagen and MMP-9 protein expression. To assess collagen content and cross-linking, two-photon excitation fluorescence imaging was performed and identified an increase in collagen abundance, but a trend towards lower collagen cross-linking in the LV of BMP9-/- mice compared to WT mice 2 weeks after MI. Our central finding is that loss of BMP9 is associated with reduced survival, increased propensity towards cardiac rupture, and increased LV collagen abundance, but reduced collagen integrity in a murine model of acute MI. These identify a potentially important functional role for BMP9 in post-infarct cardiac remodeling.

Thymosin β4: A Multi-Faceted Tissue Repair Stimulating Protein in Heart Injury.

Thymosin Beta-4 (Tβ4) is known as a major pleiotropic actin-sequestering protein that is involved in tumorigenesis. Tβ4 is a water-soluble protein that has different promising clinical applications in the remodeling and ulcerated tissues repair following myocardial infarction, stroke, plasticity and neurovascular remodeling of the Peripheral Nervous System (PNS) and the Central Nervous System (CNS). On the other hand, similar effects have been observed for Tβ4 in other kinds of tissues, including cardiac muscle tissue. In recent reports, as it activates resident epicardial progenitor cells and modulates inflammatory-caused injuries, Tβ4 has been suggested as a promoter of the survival of cardiomyocytes. Furthermore, Tβ4 may act in skeletal muscle and different organs in association/synergism with numerous other tissue repair stimulating factors, including melatonin and C-fiber-derived peptides. For these reasons, the present review highlights the promising role of Tβ4 in cardiac healing.

Cardiac fibroblast activation protein density indicative of cardiovascular disease and remodeling

Abstract Background Fibroblast activation protein (FAP) plays an important role in cardiac wound healing and remodelling. Although initially developed as a theranostic ligand for metastasized cancer, FAPI tracers have recently been used to study cardiac remodelling following myocardial infarction in small animal models. Aim of our analysis was to evaluate the activity of fibroblast activation protein via (FAPI) PET-CT scans in human hearts. Methods FAPI-PET-CT scans of 229 patients of two consecutive cohorts (initial cohort: n=185; confirmatory cohort: n=44) suffering from metastasized cancer were analysed using a 17-segment model of the left ventricle. Patient characteristics included age, sex, cancer entity, body mass index, renal function, thyroid stimulating hormone, cardiovascular risk factors, previous radiation to the chest, chemotherapies received, and current cardiac medication. Multivariate regression models were created using data from the initial cohort by selecting variables according to Akaike's information criterion in a step-down approach. Linear regression models were used for signal prediction to find potential outliers with unexpectedly high signal intensities. The created models were subsequently evaluated in the confirmatory cohort for reproducibility. Results Signal intensity were significantly higher in patients with overweight, diabetes and following radiation to the chest. Our prediction model performed well in both cohorts. A focal enrichment pattern was more frequently observed in patients with known cardiovascular risk factors. Conclusions FAPI-PET-CT scans represent a new imaging modality to potentially investigate active cardiac remodelling. High signal intensities are associated with cardiovascular risk factors and metabolic disease. Furthermore, high cardiac FAPI signal intensities are suggestive of an underlying cardiac disease. Funding Acknowledgement Type of funding source: None

ATP-Sensitive Potassium Channels Mediate the Cardioprotective Effect of Panax notoginseng Saponins against Myocardial Ischaemia-Reperfusion Injury and Inflammatory Reaction.

Inflammatory response during myocardial ischemia reperfusion injury (MIRI) is essential for cardiac healing, while excessive inflammation extends the infarction and promotes adverse cardiac remodeling. Understanding the mechanism of these uncontrolled inflammatory processes has a significant impact during the MIRI therapy. Here, we found a critical role of ATP-sensitive potassium channels (KATP) in the inflammatory response of MIRI and its potential mechanism and explored the effects of Panax Notoginseng Saponins (PNS) during this possess. Rats underwent 40 min ischemia by occlusion of the left anterior descending (LAD) coronary artery and 60 min of reperfusion. PNS was treated at the corresponding time point before operation; 5-hydroxydecanoate (5-HD) and glybenclamide (Gly) (or Nicorandil (Nic)) were used as pharmacological blocker (or nonselective opener) of KATP. Cardiac function and pathomorphology were evaluated and a set of molecular signaling experiments was tested. KATP current density was measured by patch-clamp. Results revealed that in MIRI, PNS pretreatment restored cardiac function, reduced infarct size, and ameliorated inflammation through KATP. However, inhibiting KATP by 5-HD and Gly significantly reversed the effects, including NLRP3 inflammasome and inflammatory mediators IL-6, MPO, TNF-α, and MCP-1. Moreover, PNS inhibited the phosphorylation and nuclear translocation of NF-κB in I/R myocardium when the KATP was activated. Importantly, PNS promoted the expression of subunits and activation of KATP. The study uncovered KATP served as a new potential mechanism during PNS modulating MIRI-induced inflammation and promoting injured heart recovery. The manipulation of KATP could be a potential therapeutic approach for MIRI and other inflammatory diseases.

Master Program in Physical Cardiochemistry

Background: The heart acting analysis leads to necessity of total energy quantization needful for its life from the cellular metabolism (Keith Flack node).
 This energy is mainly distributed to make possible the cardiac muscle acting (Electrocardiogram) and to circulate the blood in aorta to be ultimately poured out the small circulation in upstream of general circulation, distribution obeying Lusamba diagram. A model has been elaborated to choose a thermodynamic system (KUNYIMA Chart) on which the needful energy of blood flow has been assessed. It stays to quantify the vital energy for the electrification of cardiac muscle (ECG) in order to have a definitive idea on total energy from Keith Flack node. Each heart failure demands energetic knowledge of Keith Flack node and the energetic repartition of ventricles shrinkages.
 Aim and Objective: Presentation master program in cardiochemistry (new discipline) and Lusamba diagram to scientific world.
 Methodology: Observation, documentary research and calculations have been used.
 Results: Physico-chemical and thermoexergetic grounds of heart acting have been published elsewhere and allowed thus to conceive this program.
 Conclusion: Physical Cardiochemistry (PCC) is therefore a set of physico-chemical and thermoexergetic grounds of heart acting. It backs up the bio-medical sciences and helps in one sense to the comprehension of certain energetic phenomena occurring in the cardiac system. Therefore, this large knowledge will help physicians to efficient prescriptions for an effective energetic and appropriate supplying. It is supposed evidently that future cardiac healing will essentially be energetic.

Relationship Between Cardiac Fibroblast Activation Protein Activity by Positron Emission Tomography and Cardiovascular Disease.

FAP (fibroblast activation protein) plays an important role in cardiac wound healing and remodeling. Although initially developed as a theranostic ligand for metastasized cancer, FAPI (FAP inhibitor) tracers have recently been used to study cardiac remodeling following myocardial infarction in small-animal models. The aim of the study was to evaluate the activity of FAP via FAPI-positron emission tomography-computed tomography scans in human hearts. FAPI-positron emission tomography-computed tomography scans of 229 patients of 2 consecutive cohorts (modeling cohort: n=185; confirmatory cohort: n=44) suffering from metastasized cancer were analyzed applying the American Heart Association 17-segment model of the left ventricle. Logistic regression models were created using data from the modeling cohort. Multivariate regression models were established using Akaike information criterion in a step-down approach. Fourteen percent of patients had preexisting coronary artery disease (n=31), 33% arterial hypertension (n=75), and 12% diabetes mellitus type II (n=28). Forty-three percent had been treated with platin derivatives (n=100), 14% with anthracyclines (n=32), and 10% had a history of prior radiation to the chest (n=23). High left ventricular FAPI signals correlated with the presence of cardiovascular risk factors (odds ratio [OR], 4.3, P=0.0029), a focal myocardial signal pattern (OR, 3.9, P=0.0068), diabetes mellitus type II (OR, 4.1, P=0.046), and beta-blocker use (OR, 3.8, P=0.049) in univariate regression models. In a multivariate analysis, increased signal intensity was significantly higher in patients with cardiovascular risk factors (overweight [OR, 2.6, P=0.023], diabetes mellitus type II [OR, 2.9, P=0.041], certain chemotherapies [platinum derivatives; OR, 3.0, P=0.034], and a history of radiation to the chest [OR, 3.5, P=0.024]). A focal enrichment pattern was more frequently observed in patients with known cardiovascular risk factors (P<0.0001). FAPI-positron emission tomography-computed tomography scans represent a new imaging modality to investigate cardiac FAP. High signal intensities correlate with cardiovascular risk factors and metabolic disease.

Abstract 302: IL4Ra is Required for Cardiomyocyte Cell Cycle Activity and Cardiac Regeneration

Introduction: During the first week of life, neonatal mice are able to regenerate their hearts after injury with minimal scarring. Work from our lab demonstrates that IL13 signaling is required for neonatal heart regeneration, however multiple IL13 receptors exist. Here, we aim to identify the specific receptor ligand interaction that promotes regenerative healing in the heart. In vitro data suggests the IL4Ra/IL3Ra1 receptor heterodimer may mediate cardiomyocyte (CM) proliferation and heart regeneration. Thus, we aim to test the functional role of this receptor in cardiac regeneration in vivo . We hypothesize that IL13 signals through IL4Ra/IL13Ra1 directly on CMs to promote CM cell cycle activity and cardiac regeneration. Methods: To delineate IL13 signaling mechanisms in murine hearts, we utilized two knockouts of IL4Ra—global IL4Ra knockout (KO) and CM-specific IL4Ra knockout (IL4Ra fl/fl Myh6 CRE ) mice. To assess regeneration, mice received cardiac apical resection surgery at postnatal day 1 (P1). Regeneration was assessed by echocardiography and histological analysis of residual scars and CM proliferation indices. We next tested if IL13 administration could extend the regenerative window. We performed myocardial infarction (MI) on P7 mice and administered IL13 for two weeks. We assessed scar size through trichrome staining and CM cell cycle activity through immunostaining. Results: We observed impaired cardiac regeneration, determined by scar formation and decreased cardiac function in IL4Ra KO mice compared to littermate controls. Similar to global KOs, we observed decreased function in IL4Ra fl/fl Myh6 CRE mice. IL13 administration to wildtype mice after P7 MI decreased MI severity and increased CM cell cycle activity, suggesting improved reparative capacity. Interestingly, IL13 administration in IL4Ra fl/fl Myh6 CRE mice did not improve cardiac recovery phenotypes indicating that IL13 functions through IL4Ra directly on CMs to promote cardiac healing. Conclusion: These results demonstrate that the IL4Ra receptor subunit is required for cardiac regeneration, and activation of this receptor can extend the regenerative window. These findings lay the groundwork for potential therapeutic targets for promoting cardiac healing.

Two Sides of Electrospun Fiber in Promoting and Inhibiting Biomedical Processes

AbstractElectrospinning is a versatile technique for generating ultrathin fibers, which is widely applied in various biomedical applications. The properties and structures of the fibers are specifically engineered to meet the needs of particular applications. The impact of nanofibrous scaffolds on biological processes is related to the promotion or inhibition of specific cell or bioactive substance functions. Here, a novel analysis of the diverse roles of electrospun nanofibrous scaffolds is provided and recent advances in exploiting their binary attributes for applications in biomedicine are summarized. This review initially introduces the development techniques for electrospinning, specifically the engineering of electrospun nanofibers. Then, scaffold applications for cell migration, adhesion, proliferation, and accelerating regeneration in cardiac, nerve, skeletal muscle, bone tissue, and wound healing are presented. Moreover, their inhibitory properties in cancer treatments, antibacterial applications, anti‐adhesion, anti‐scarring, and inhibition of thrombus formation are summarized. Eventually, the potential for future work using multifunctional, electrospun, nanofibrous scaffolds, in order to further inspire the development of scaffolds for biomedical treatments is summarized and discussed.

Macrophage Efferocytosis in Cardiac Pathophysiology and Repair.

As an integral component of cardiac tissue, macrophages are critical for cardiac development, adult heart homeostasis, as well as cardiac healing. One fundamental function of macrophages involves the clearance of dying cells or debris, a process termed efferocytosis. Current literature primarily pays attention to the impact of efferocytosis on apoptotic cells. However, emerging evidence suggests that necrotic cells and their released cellular debris can also be removed by cardiac macrophages through efferocytosis. Importantly, recent studies have demonstrated that macrophage efferocytosis plays an essential role in cardiac pathophysiology and repair. Therefore, understanding macrophage efferocytosis would provide valuable insights on cardiac health, and may offer new therapeutic strategies for the treatment of patients with heart failure. In this review, we first summarize the molecular signals that are associated with macrophage efferocytosis of apoptotic and necrotic cells, and then discuss how the linkage of efferocytosis to the resolution of inflammation affects cardiac function and recovery under normal and diseased conditions. Lastly, we highlight new discoveries related to the effects of macrophage efferocytosis on cardiac injury and repair.

Synergistic Fabrication of Dose-Response Chitosan/Dextran/β-Glycerophosphate Injectable Hydrogel as Cell Delivery Carrier for Cardiac Healing After Acute Myocardial Infarction.

The human mesenchymal stem cells (hMSCs) therapy offering an encouraging the new methods to establish the conveying on the chitosan (C)/dextran (D)/β-glycerophosphate (β-GP) loaded with hMSCs to enhance the acute myocardial infarctions. The synthesized hMSCs-CD@β-GP system displayed the ratio of determination modules, size of the pore, absorbency, and the swellings ratio in the assortment of the 65 ka, 149 ± 39.8 µm, 92.2%, 42 ± 1.38, and 29 ± 1.9, respectively. The fabricated hMSCs-CD@β-GP was highly stable and physicochemical investigated and confirmed the suitability of the materials for cardiac regeneration applications. The in vitro examinations of the injectable hydrogels with hMSCs-CD@β-GP have recognized that the improved survival rate of the cells, increased the pro-inflammatory expressions factors, pro-angiogenic factors analysis confirmed the promising results of the ejection of fractions, fibrosis area, vessel density with decreased infractions size, with suggesting that the remarkable improvement of the heart regenerative function after myocardial infarctions. The new synergistic approach of the injectable hydrogels with hMSCs could able appropriate for the effective treatment of cardiac therapies after acute myocardial infarctions.

Bauhinia purpurea: An Updated Pharmacological Profile

Bauhinia purpurea (B. purpurea) (family: Fabaceae) commonly called as butter fly tree has vast medicinal uses and remarkable pharmacological potential. Various phytoconstituents, extracts and parts of this plant were possess significant pharmacological activities such as cardiac activity, antifungal, wound healing, antidiabetic, antiulcer, antioxidant, antinociceptive, hepatoprotective, nephroprotective, antidiarrhoeal, anti-inflammatory, antipyretic, analgesic, antimalarial, gastro protective and cytoprotective activity. The present study emphasizes the overview of recent studies and/or updates on pharmacological potential of B. purpurea.

Cardiac fibroblast activation during myocardial infarction wound healing: Fibroblast polarization after MI

Cardiac wound healing after myocardial infarction (MI) evolves from pro-inflammatory to anti-inflammatory to reparative responses, and the cardiac fibroblast is a central player during the entire transition. The fibroblast mirrors changes seen in the left ventricle infarct by undergoing a continuum of polarization phenotypes that follow pro-inflammatory, anti-inflammatory, and pro-scar producing profiles. The development of each phenotype transition is contingent upon the MI environment into which the fibroblast enters. In this mini-review, we summarize our current knowledge regarding cardiac fibroblast activation during MI and highlight key areas where gaps remain.

Stimulating pro-reparative immune responses to prevent adverse cardiac remodelling: consensus document from the joint 2019 meeting of the ESC Working Groups of cellular biology of the heart and myocardial function.

Cardiac injury may have multiple causes, including ischaemic, non-ischaemic, autoimmune, and infectious triggers. Independent of the underlying pathophysiology, cardiac tissue damage induces an inflammatory response to initiate repair processes. Immune cells are recruited to the heart to remove dead cardiomyocytes, which is essential for cardiac healing. Insufficient clearance of dying cardiomyocytes after myocardial infarction (MI) has been shown to promote unfavourable cardiac remodelling, which may result in heart failure (HF). Although immune cells are integral key players of cardiac healing, an unbalanced or unresolved immune reaction aggravates tissue damage that triggers maladaptive remodelling and HF. Neutrophils and macrophages are involved in both, inflammatory as well as reparative processes. Stimulating the resolution of cardiac inflammation seems to be an attractive therapeutic strategy to prevent adverse remodelling. Along with numerous experimental studies, the promising outcomes from recent clinical trials testing canakinumab or colchicine in patients with MI are boosting the interest in novel therapies targeting inflammation in cardiovascular disease patients. The aim of this review is to discuss recent experimental studies that provide new insights into the signalling pathways and local regulators within the cardiac microenvironment promoting the resolution of inflammation and tissue regeneration. We will cover ischaemia- and non-ischaemic-induced as well as infection-related cardiac remodelling and address potential targets to prevent adverse cardiac remodelling.

T-cell regulation of fibroblasts and cardiac fibrosis

Inflammation contributes to the development of heart failure (HF) through multiple mechanisms including regulating extracellular matrix (ECM) degradation and deposition. Interactions between cells in the myocardium orchestrates the magnitude and duration of inflammatory cell recruitment and ECM remodeling events associated with HF. More recently, studies have shown T-cells have signficant roles in post-MI wound healing. T-cell biology in HF illustrates the complexity of cross-talk between inflammatory cell types and resident fibroblasts. This review will focus on T-cell recruitment to the myocardium and T-cell specific factors that might influence cardiac wound healing and fibrosis in the heart with consideration of age and sex as important factors in T-cell activity.

Volumetric Optoacoustic Tomography Differentiates Myocardial Remodelling.

Myocardial healing following myocardial infarction (MI) is a complex process that is yet to be fully understood. Clinical attempts in regeneration of the injured myocardium using cardiac stem cells faced major challenges, calling for a better understanding of the processes involved at a more basic level in order to foster translation. We examined the feasibility of volumetric optoacoustic tomography (VOT) in studying healing of the myocardium in different models of MI, including permanent occlusion (PO) of the left coronary artery, temporary occlusion (ischemia-reperfusion-I/R) and infarcted c-kit mutants, a genetic mouse model with impaired cardiac healing. Murine hearts were imaged at 100Hz frame rate using 800nm excitation wavelength, corresponding to the peak absorption of indocyanine green (ICG) in plasma and the isosbestic point of haemoglobin. The non-invasive real-time volumetric imaging capabilities of VOT have allowed the detection of significant variations in the pulmonary transit time (PTT), a parameter affected by MI, across different murine models. Upon intravenous injection of ICG, we were able to track alterations in cardiac perfusion in I/R models, which were absent in wild-type (wt) PO or kitW/kitW-v PO mice. The wt-PO and I/R models further exhibited irregularities in their cardiac cycles. Clear differences in the PTT, ICG perfusion and cardiac cycle patterns were identified between the different models and days post MI. Overall, the results highlight the unique capacity of VOT for multi-parametric characterization of morphological and functional changes in murine models of MI.

Extracellular vesicles from human embryonic stem cell-derived cardiovascular progenitor cells promote cardiac infarct healing through reducing cardiomyocyte death and promoting angiogenesis

Human pluripotent stem cells (hPSCs)-derived cardiovascular progenitor cells (CVPCs) are a promising source for myocardial repair, while the mechanisms remain largely unknown. Extracellular vesicles (EVs) are known to mediate cell–cell communication, however, the efficacy and mechanisms of hPSC-CVPC-secreted EVs (hCVPC-EVs) in the infarct healing when given at the acute phase of myocardial infarction (MI) are unknown. Here, we report the cardioprotective effects of the EVs secreted from hESC-CVPCs under normoxic (EV-N) and hypoxic (EV-H) conditions in the infarcted heart and the long noncoding RNA (lncRNA)-related mechanisms. The hCVPC-EVs were confirmed by electron microscopy, nanoparticle tracking, and immunoblotting analysis. Injection of hCVPC-EVs into acutely infracted murine myocardium significantly improved cardiac function and reduced fibrosis at day 28 post MI, accompanied with the improved vascularization and cardiomyocyte survival at border zones. Consistently, hCVPC-EVs enhanced the tube formation and migration of human umbilical vein endothelial cells (HUVECs), improved the cell viability, and attenuated the lactate dehydrogenase release of neonatal rat cardiomyocytes (NRCMs) with oxygen glucose deprivation (OGD) injury. Moreover, the improvement of the EV-H in cardiomyocyte survival and tube formation of HUVECs was significantly better than these in the EV-N. RNA-seq analysis revealed a high abundance of the lncRNA MALAT1 in the EV-H. Its abundance was upregulated in the infarcted myocardium and cardiomyocytes treated with hCVPC-EVs. Overexpression of human MALAT1 improved the cell viability of NRCM with OGD injury, while knockdown of MALAT1 inhibited the hCVPC-EV-promoted tube formation of HUVECs. Furthermore, luciferase activity assay, RNA pull-down, and manipulation of miR-497 levels showed that MALAT1 improved NRCMs survival and HUVEC tube formation through targeting miR-497. These results reveal that hCVPC-EVs promote the infarct healing through improvement of cardiomyocyte survival and angiogenesis. The cardioprotective effects of hCVPC-EVs can be enhanced by hypoxia-conditioning of hCVPCs and are partially contributed by MALAT1 via targeting the miRNA.

Macrophage Activities in Myocardial Infarction and Heart Failure.

Heart diseases remain the major cause of death worldwide. Advances in pharmacological and biomedical management have resulted in an increasing proportion of patients surviving acute heart failure (HF). However, many survivors of HF in the early stages end up increasing the disease to chronic HF (CHF). HF is an established frequent complication of myocardial infarction (MI), and numerous influences including persistent myocardial ischemia, shocked myocardium, ventricular remodeling, infarct size, and mechanical impairments, as well as hibernating myocardium trigger the development of left ventricular systolic dysfunction following MI. Macrophage population is active in inflammatory process, yet the clear understanding of the causative roles for these macrophage cells in HF development and progression is actually incomplete. Long ago, it was thought that macrophages are of importance in the heart after MI. Also, though inflammation is as a result of adverse HF in patients, but despite the fact that broad immunosuppression therapeutic target has been used in various clinical trials, no positive results have showed up, but rather, the focus on proinflammatory cytokines has proved more benefits in patients with HF. Therefore, in this review, we discuss the recent findings and new development about macrophage activations in HF, its role in the healthy heart, and some therapeutic targets for myocardial repair. We have a strong believe that there is a need to give maximum attention to cardiac resident macrophages due to the fact that they perform various tasks in wound healing, self-renewal of the heart, and tissue remodeling. Currently, it has been discovered that the study of macrophages goes far beyond its phagocytotic roles. If researchers in future confirm that macrophages play a vital role in the heart, they can be therapeutically targeted for cardiac healing.

LOW LEVEL OF HIGH SENSITIVITY C-REACTIVE PROTEIN AFTER PERCUTANEOUS CORONARY INTERVENTION PREDICTS RISK OF DEATH IN PATIENTS WITH MYOCARDIAL INFARCTION

Suppressing acute inflammation after myocardial infarction (MI) is gaining greater interest, but remained controversial due to concerns on delaying cardiac healing. Impacts of inflammation after MI require further illustration. A retrospective cohort was formed with 3980 consecutive MI patients