Cardiovascular (CV) disease is the leading cause of mortality in systemic lupus erythematosus (SLE). The risk of myocardial infarction (MI) in SLE is twice the incidence and ten years earlier in onset than in the general population. We present the first known case in the Philippines of acute MI from triple vessel coronary artery disease (CAD) in a young female patient with SLE. This aims to increase recognition and improve preventive strategies for this rare lupus complication. A 31-year-old female with SLE for thirteen years, antiphopspholipid syndrome (APS) and controlled hypertension (HTN) presented with acute chest pain, diaphoresis, and dyspnea. She was a non-smoker with quiescent lupus and nephritis, maintained on low-dose aspirin, mycophenolate mofetil and hydroxychloroquine for the past four years. The physical examination revealed hypertension, bradycardia, normal heart sounds without murmurs, and no signs of lupus flare. The troponin level was elevated, and the electrocardiogram showed inferior wall ST-segment elevation myocardial infarction (STEMI). Coronary angiography revealed triple-vessel disease, with 80-90% stenosis of the left circumflex artery, and total occlusion of the left anterior descending and right coronary artery. There were segmental wall motion abnormalities and a low ejection fraction of 44% on echocardiography. The complete blood count, urinalysis, and serum C3 were within normal range. The anti-dsDNA was low and lipid levels were abnormal. The patient refused coronary artery bypass grafting (CABG). Medical management consisting of anti-platelets, beta-blockers, statin, and warfarin was maximized. The patient completed one year of follow-up without any lupus flares or cardiovascular events. This case illustrates the complex interaction of disease-related and traditional cardiovascular risk factors leading to premature coronary artery disease in a young female with SLE. The case demonstrates favorable one-year outcomes after optimized post-MI medical management. Aside from optimized lupus control and reduced glucocorticoid use, proactive screening and aggressive management of modifiable CV risk factors and antiphospholipid antibodies (aPL), are necessary.
Human ; Female ; Adult: 25-44 Yrs Old ; Lupus Erythematosus, Systemic ; Myocardial Infarction ; Literature ; Infarction ; Female

INTRODUCTION

Acute coronary syndrome (ACS) and end-stage renal disease (ESRD) are both prevalent globally. The diagnosis and management of ACS in ESRD is difficult because the interplay of cardiovascular and renal disease is complicated. The guidelines for ACS may not be applicable to the ESRD population because the trials from which these are drawn mostly excluded ESRD patients.

To determine the clinical profile and outcomes of CKD patients on dialysis admitted for ACS in the Philippine General Hospital (PGH).

We did a retrospective cohort study and employed a retrospective review of electronic medical records among ESRD patients presenting with ACS in PGH from May 2021 to November 2023. The collected data was analyzed using univariate and bivariate statistics using PRISM software.

A total of 48 patients with ESRD were admitted for ACS in this study – 8 with STEMI and 40 with NSTEMI. The mean age was 61 years old and 33 (68.8%) were male. Among those with STEMI, six (75%) presented with Kilip II or more. While among those with NSTEMI, 17 (42.5%) had a GRACE score >140 and 27 (67.5%) had an NSTEMI TIMI risk score >2. On average, the patients were on hemodialysis for 31 months prior to admission. The most common comorbidities were hypertension (91.7%) and heart failure (83.3%). On admission, 18 (37.5%) presented with SBP >160, 7 (14.6%) patients presented with shock, and 4 (8.3%) patients presented with cardiac arrest. 38 (79.2%) patients had anemia on admission. 21 (43.8%) patients had left ventricular hypertrophy on electrocardiogram while 34 (70.8%) patients had cardiomegaly on chest radiography. The average left ventricular ejection fraction on echocardiogram was 46% and 27 (90%) patients had segmental wall motion abnormalities. The most common angiographic finding was 3-vessel coronary artery disease seen in 50% of patients. Almost all patients received dualantiplatelet therapy, high dose statin, and beta-blocker. The mortality rate was high at 43.8% with cardiovascular causes being the most common cause of death.

This study demonstrates the high mortality rate among patients with ESRD presenting with ACS. Our study portrays that patients with ESRD present with higher risk features including abnormalities in vital signs, laboratories, imaging, high prognostications score, and high in-hospital morbidity.

INTRODUCTION

Takayasu arteritis (TA) is a rare chronic large vessel vasculitis that affects the aorta and its major branches with a median age of onset of 25 years. The disease has a worldwide incidence of 1-2 per million, primarily affecting females with a 9:1 ratio. It is considered as an autoimmune disease that leads to progressive vessel thickening and stenosis, or aneurysmal dilatation. Coronary artery involvement is observed in 5.9%-58.2% of TA cases. We present a case of TA in a Filipino male presenting concurrently with myocardial infarction (MI) and ischemic stroke.

A 41-year-old Filipino male smoker with hypertension presented with chest pain, left-sided paresthesia and hemiparesis. Initial assessment revealed differential blood pressure between the arms, sensory and motor deficits, and abnormal ABI. Electrocardiogram confirmed anteroseptal ST-elevation MI and cranial computed tomography (CT) showed ischemic stroke. Arterial duplex scan had findings suggestive of hemodynamically significant lower extremity stenosis. A CT aortogram revealed multiple occlusions, including in the left subclavian artery, suggesting TA. Coronary angiography was attempted but was deferred due to peripheral arterial occlusion. A CT coronary angiogram revealed severe stenosis of the left anterior descending artery and moderate stenosis of the other coronaries. The patient was treated with dual antiplatelet therapy, statins, anticoagulation, corticosteroids and methotrexate. He experienced significant improvement in neurological symptoms and was chest pain-free upon discharge. At the 1-month follow-up, the patient remained asymptomatic.

Coronary involvement in TA can manifest as angina, MI, or other coronary lesions. The coexistence of MI and ischemic stroke in the same event is rare. Traditional risk factors for ischemic heart disease (IHD) in this patient such as hypertension and smoking may have contributed to the presentation, though TA itself is known to accelerate atherosclerosis. Limited vascular access hindered coronary intervention in this case and revascularization strategies remain challenging in active TA. The formation of extensive collateral arteries, along with early initiation of immunosuppressive therapy, likely contributed to the patient’s survival.

This case illustrates a rare and complex case of TA in a male patient with concurrent MI and ischemic stroke. Although coronary revascularization was not pursued due to occluded access, immunosuppressive therapy successfully managed the patient’s condition. Extensive collateral artery formation and early therapeutic intervention were key factors in the patient’s favorable outcome.

INTRODUCTION

The existence of a coronary artery aneurysm (CAA) can pose significant risk for death. It can cause thrombosis, dissection, rupture or myocardial infarction. An exceedingly rare involvement of the left main coronary artery (LMCA), particularly giant-sized is even more catastrophic, a finding seen in only 0.1% of patients. Furthermore, co-existence with significant stenotic coronary artery disease (CAD) portends grim survival. Owing to the rarity of this combination, no data is available locally and only limited case reports are documented internationally. Hence, no consensus guidelines have been published yet. This paper aims to contribute to the sparse medical knowledge on the treatment approach and management of LMCA aneurysm with concomitant CAD.

A 62-year-old male, Filipino, hypertensive and hyperlipidemic sought consult due to one-year exertional chest pain. Coronary angiogram revealed the LMCA to be a diffusely aneurysmal, large-sized vessel measuring 9.7 mm x 7.9 mm with a significant two-vessel CAD affecting the proximal left anterior descending (LAD) and right coronary artery (RCA). As per multidisciplinary decision, the patient underwent surgical revascularization via cardiopulmonary bypass graft (CABG) addressing the CAD and LMCA aneurysm managed conservatively through guideline-directed medical therapy. The patient’s course of treatment was uneventful. He returned for follow-ups for three months post-surgery and remained symptom-free.

Giant coronary artery aneurysms (GCAA) are vessel dilatations that exceed 4x the diameter of a normal adjacent artery. The patient had a unique case of GCAA involving the LMCA combined with two-vessel CAD. Few studies have documented a medical or surgical approach and long-term outcomes are unknown. Without sufficient evidence-based guidelines, the multidisciplinary decision was to perform CABG and manage the LMCA aneurysm conservatively.

Due to extremely limited information available on the giant LMCA aneurysm natural history, definitive management remains controversial. A multidisciplinary team approach is highly recommended for patient-specific needs to achieve favorable outcome and ensure survival.

The autonomic nervous system imbalance caused by the overactivation of the sympathetic nerve and the weakened activity of the parasympathetic nerve is closely related to the occurrence and development of myocardial infarction.Autonomic nerve regulation is a new therapeutic approach aiming at inhibiting sympathetic activity and increasing parasympathetic activity.It encompasses magnetic nerve stimulation,optogenetic neuromodulation,and microinjection of botulinum toxin,which could promote the rebalance of the autonomic nervous system,thereby curbing the deterioration of the cardiac function and reducing the occurrence of ventricular arrhythmias after myocardial infarction.This paper reviews the anatomical basis,mechanisms of action,and research advances in intervention strategies of the autonomic nervous system in myocardial infarction.
Humans ; Myocardial Infarction/physiopathology* ; Autonomic Nervous System/physiopathology* ; Autonomic Pathways

Objective To identify disulfidptosis-related gene(DRG)in acute myocardial infarction(AMI)by bioinformatics,analyze the molecular pattern of DRGs in AMI,and construct a DRGs-related prediction model.Methods AMI-related datasets were downloaded from the Gene Expression Omnibus database,and DRGs with differential expression were screened in AMI.CIBERSORT method was used to analyze the immune infiltration.Based on the differentially expressed DRGs,the AMI patients were classified into distinct subtypes via consensus clustering,followed by immune infiltration analysis,differential expression analysis,gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis,and gene set variation analysis.Weighted gene co-expression network analysis(WGCNA)was then performed to construct subtype-associated modules and identify hub genes.Finally,least absolute shrinkage and selection operator,random forest,and support vector machine-recursive feature elimination were used to screen feature genes to construct a DRGs-related prediction model.The model's diagnostic efficacy was evaluated by nomogram and receiver operating characteristic(ROC)curve analysis,followed by external validation.Results Nine differentially expressed DRGs were identified between AMI patients and controls.Based on the expression levels of these nine DRGs,AMI patients were divided into two DRGs subtypes,C1 and C2.Increased infiltration of monocytes,M0 macrophages,and neutrophils was observed in AMI patients and C1 subtype(all P<0.05),indicating a close correlation between DRGs and immune cells.There were 257 differentially expressed genes between the C1 and C2 subtypes,which were related to biological processes such as myeloid leukocyte activation and positive regulation of cytokines.Fcγ receptor-mediated phagocytosis and NOD-like receptor signaling pathway activity were enhanced in C1 subtype.WGCNA analysis suggested that the brown module exhibited the strongest correlation with DRG subtypes(r=0.67),from which 23 differentially expressed genes were identified.The feature genes screened by three machine learning methods were interpolated to obtain a DRGs-related prediction model consisting of three genes(AQP9,F5 and PYGL).Nomogram and ROC curves(AUC_train=0.891,AUC_test=0.840)showed good diagnostic efficacy.Conclusions DRGs were closely related to the occurrence and progression of AMI.The DRGs-related prediction model consisting of AQP9,F5 and PYGL may provide targets for the diagnosis and personalized treatment of AMI.
Humans ; Myocardial Infarction/diagnosis* ; Transcriptome ; Computational Biology ; Gene Expression Profiling ; ROC Curve ; Gene Regulatory Networks ; Nomograms ; Disulfidptosis

Objective To explore the mechanism of lncRNA-BC200 (BC200) targeting the ubiquitination of Beta-site APP cleaving enzyme 1 (BACE1) and regulating the repair of nerve cell injury. Methods Mouse hippocampal neuron cell line HT22 was divided into four groups: control group, oxygen-glucose deprivation/reoxygenation(OGD/R) group, OGD/R+si-NC group and OGD/R+si-BC200 group. In order to further explore the relationship between BC200 and BACE1, HT22 cells were divided into four groups: OGD/R group, OGD/R+si-BC200 group, OGD/R+si-BC200+NC group and OGD/R+si-BC200+ BACE1 group. Twenty male C57BL/6J mice were randomly assigned to the following four groups: control group, middle cerebral artery occlusion (MCAO) group, MCAO+si-BC200 group and MCAO+si-BC200+BACE1 group. The mRNA expression levels of BC200 and BACE1 in cells were measured by real-time quantitative reverse transcription polymerase chain reaction. The expressions of c-caspase-3, B-cell lymphoma 2 (Bcl2), Bcl2 associated X protein(BAX) and BACE1 were detected by western blot, and the apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Results Compared with the control group, the activity of HT22 cells in OGD/R group decreased significantly, and the percentage of apoptotic cells increased significantly. Compared with OGD/R+si-NC group, the activity of HT22 cells in OGD/R+si-BC200 group increased significantly, and the percentage of apoptotic cells decreased significantly. Compared with the control group, the expression of BACE1 protein in HT22 cells in OGD/R group was significantly enhanced. Compared with OGD/R+si-NC group, the expression of BACE1 protein in HT22 cells in OGD/R+si-BC200 group decreased significantly. It was observed that after OGD/R treatment, the ubiquitination level of BACE1 decreased significantly and the expression of BACE1 protein increased significantly. After transfection with si-BC200, the ubiquitination level of BACE1 protein increased significantly, while the expression of BACE1 protein decreased significantly. Compared with OGD/R+si-BC200+NC group, the percentage of apoptotic cells, the expression of c-caspase-3 and Bax protein in HT22 cells in OGD/R+si-BC200+BACE1 group increased significantly, and the expression of Bcl2 protein decreased significantly. Compared with the control group, the number of cerebral infarction areas and TUNEL positive cells in MCAO group increased significantly, and the survival number of neurons decreased significantly. Compared with the MCAO group, the number of cerebral infarction areas and TUNEL positive cells in MCAO+si-BC200 group decreased significantly, and the survival number of neurons increased significantly, while the addition of BACE1 reversed the improvement of si-BC200 transfection. Conclusion The combination of BC200 and BACE1 inhibit the ubiquitination of BACE1, and participate in mediating the expression enhancement of BACE1 induced by OGD/R. Specific blocking of BC200/BACE1 axis may be a potential therapeutic target to protect neurons from apoptosis induced by cerebral ischemia/reperfusion.
Animals ; Amyloid Precursor Protein Secretases/genetics* ; RNA, Long Noncoding/physiology* ; Aspartic Acid Endopeptidases/genetics* ; Male ; Neurons/pathology* ; Mice ; Mice, Inbred C57BL ; Apoptosis/genetics* ; Ubiquitination ; Cell Line ; Hippocampus/metabolism* ; bcl-2-Associated X Protein/genetics* ; Caspase 3/genetics* ; Infarction, Middle Cerebral Artery/metabolism*

Objective To investigate the impact of Astragaloside-IV (AS-IV) on the progression of myocardial infarction (MI) through macrophage-dependent mechanisms by regulating Snail1 lactylation and acetylation, as well as the transforming growth factor β (TGF-β) pathway. Methods Oxygen glucose deprivation (OGD) was used to establish an in vitro myocardial ischemia model in rat cardiomyocytes (H9c2), which were then treated with AS-IV. Cell viability was assessed using CCK-8, apoptosis was evaluated by flow cytometry, and LDH levels were measured to assess cellular damage. RAW246.7 cells were treated with LPS, and lactate levels in the supernatant were measured using ELISA, while expression of macrophage phenotype markers was evaluated using Western blot. RAW246.7 cell-conditioned medium (CM) was co-cultured with H9c2 cells to assess the protective effects of AS-IV on macrophage CM-mediated H9c2 damage. RAW246.7 cells were induced to differentiate into M1-like macrophages using LPS (100 ng/mL) + IFN-γ (20 ng/mL), and Snail1 was overexpressed in M1 macrophages. Transfected M1 macrophage CM was co-cultured with H9c2 cells to validate the mechanisms of AS-IV in MI. An MI rat model was established by ligation of the left anterior descending coronary artery (LAD), and was treated with AS-IV. Cardiac function, myocardial cell apoptosis, and cardiac tissue pathology were studied using echocardiography, TUNEL, and HE staining, respectively. Results Compared to the OGD group, AS-IV treatment promoted cell viability, reduced apoptosis and decreased LDH release. LPS upregulated lactate levels in the supernatant of RAW246.7 cell cultures and induced polarization of RAW246.7 cells to the M1 phenotype. AS-IV attenuated the damaging effects of RAW246.7 cell CM on H9c2 cells . Overexpression of Snail1 in M1 macrophages weakened the protective effects of AS-IV on H9c2 cells . In vivo study, results showed that, compared to the MI group, AS-IV treatment reduced lactate levels in the hearts of MI rats, improved cardiac function and myocardial injury and attenuated myocardial cell apoptosis. Conclusion AS-IV inhibits TGF-β pathway activation through the suppression of Snail1 lactylation and acetylation in a macrophage-dependent manner, thereby mitigating myocardial cell damage following MI.
Animals ; Myocardial Infarction/drug therapy* ; Rats ; Snail Family Transcription Factors/metabolism* ; Macrophages/cytology* ; Myocytes, Cardiac/metabolism* ; Triterpenes/pharmacology* ; Saponins/pharmacology* ; Acetylation/drug effects* ; Apoptosis/drug effects* ; Mice ; Cell Line ; RAW 264.7 Cells ; Transforming Growth Factor beta/metabolism*

OBJECTIVES: To investigate the effect of Shenge powder (SGP) on myocardial fibrosis in rats with heart failure after myocardial infarction and its relation with lysyl oxidase like protein 2 (LOXL2)/transforming growth factor-β1 (TGF-β1)/IL-11 signaling pathway. METHODS: Seventy-two SPF male SD rats were divided into blank control group, model control group, SGP small dose group, SGP large dose group, positive control group, SGP large dose+LOXL2 activator group, with 12 rats in each group. Except for the blank control group, post-myocardial infarction heart failure was induced by coronary constriction. Corresponding treatments were given immediately after successful modeling, once a day for 4 weeks. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) in rats were detected by color Doppler ultrasound imaging. Levels of IL-1β and IL-6 in serum were analyzed by ELISA method. Myocardial collagen volume fraction (CVF) was evaluated by Masson staining. Expressions of collagen Ⅰ and α-smooth muscle actin (α-SMA) in myocardial tissue were detected by immunohistochemical staining. The mRNA expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in myocardial tissue were detected by qRT-PCR. Expression of LOXL2, TGF-β1, and IL-11 proteins in myocardial tissue were detected by Western blotting. RESULTS: Compared with the blank control group, the LVFS and LVEF of the model control group decreased, the levels of serum IL-6 and IL-1β elevated, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins increased (all P<0.05). Compared with the model control group, the LVFS and LVEF of SGP small dose group, SGP large dose group and positive control group increased, the levels of serum IL-6 and IL-1β decreased, and the CVF value, the expressions of collagen Ⅰ and α-SMA in myocardial tissue, MMP-9 and TIMP-1 mRNA, and LOXL2, TGF-β1, IL-11 proteins decreased (all P<0.05); while LOXL2 activator reversed the improvement effect of high-dose SGP on myocardial fibrosis in heart failure rats after myocardial infarction. CONCLUSIONS Shenge powder may inhibit myocardial fibrosis in heart failure rats after myocardial infarction by inhibiting the LOXL2/TGF-β1/IL-11 pathway.
Animals ; Male ; Rats, Sprague-Dawley ; Myocardial Infarction/complications* ; Transforming Growth Factor beta1/metabolism* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Rats ; Heart Failure/pathology* ; Myocardium/metabolism* ; Fibrosis ; Amino Acid Oxidoreductases/metabolism* ; Interleukin-11/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Matrix Metalloproteinase 9/metabolism*

Myocardial infarction is a cardiovascular disease with high morbidity and mortality rates. Hydrogel biomaterials mimicking the extracellular matrix have recently been shown to demonstrate excellent biocompatibility, low immunogenicity, favorable biodegradability, and multifunctionality, showcasing significant potential for treatment of myocardial infarction. Hydrogels can provide mechanical support to the damaged myo-cardium, alleviating pathological remodeling. Moreover, their porous structure makes them ideal carriers for localized and sustained drug delivery. Hydrogels derived from various matrices-including polysaccharides, polypeptides, proteins, decellularized extracellular matrix, and synthetic polymers-exhibit distinct properties in terms of biocompatibility, mechanical performance, and drug delivery capacity. These hydrogels support tissue regeneration and enable targeted release of diverse therapeutics, meeting the various therapeutic demands for myocardial repair. In the infarcted myocardial microenvironment, endogenous signals such as low pH, specific enzyme expression, and elevated levels of reactive oxygen species can trigger responsive drug release from hydrogels, while external physical stimuli-such as ultrasound, light, and magnetic fields-can also be employed to precisely control the release process, thereby enhancing therapeutic efficacy and reducing systemic side effects. This review summarizes recent advances in hydrogel-based drug delivery systems for treatment of myocardial infarction, focusing particularly on the characteristics and advantages of different hydrogel materials for myocardial repair. Furthermore, the responsive drug release behavior of hydrogels is analyzed in the context of the cardiac injury microenvironment, providing a reference for future research.
Hydrogels/chemistry* ; Myocardial Infarction/drug therapy* ; Humans ; Drug Delivery Systems/methods* ; Biocompatible Materials ; Drug Carriers