This article reviews the role of different types of T lymphocyte subpopulations in pathological cardiac fibrosis remodeling. T helper 17 (Th17) cells are implicated in promoting the development of pathological cardiac fibrosis remodeling, while regulatory T (Treg) cells exert an immunosuppressive functions as negative regulators, attributing to their interleukin-10 (IL-10) secretion and functional phenotype. Th1 and Th2 cells are involved in different stages of the inflammatory response in pathological cardiac fibrosis remodeling, and their influence varies according to the pathological mechanisms of different cardiac diseases. In addition, CD8⁺ T cells regulate the activation and polarization of macrophages, promote the secretion of granzyme B, induce cardiomyocyte apoptosis, and aggravate cardiac fibrosis post-myocardial infarction. Considering the limitation of cytokine modulation in clinical therapy of heart failure, targeting T-cell co-stimulatory molecules emerges as a promising strategy for treating pathologic cardiac remodeling. Future research will explore chimeric antigen receptor modified T cells (CAR-T cells) technology and targeted regulation of Treg cells quantity and phenotype, for both of which have the potential to become effective methods for treating heart disease.
Humans ; Fibrosis ; T-Lymphocytes, Regulatory/immunology* ; Ventricular Remodeling/immunology* ; Myocardium/immunology* ; Animals ; Th17 Cells/immunology* ; Interleukin-10/metabolism* ; Th1 Cells/immunology* ; Th2 Cells/immunology*

OBJECTIVE: To observe the effects of electroacupuncture (EA) pretreatment on the cardiac ejection fraction (EF), the number of macrophages in spleen and heart, and the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and interleukin-1β (IL-1β) in myocardium in mice with acute myocardial ischemia, and to explore the possible mechanism of EA pretreatment on promoting myocardial protection. METHODS: A total of 30 male C57BL/6J mice were randomly divided into a control group, a model group and an EA pretreatment group, 10 rats in each group. The acute myocardial ischemia model was established by ligating the left anterior descending branch of the coronary artery in the model group and EA pretreatment group, while threading but no ligating at left anterior descending branch of the coronary artery was applied in the control group. In the EA pretreatment group, mice were intervented with EA at bilateral "Neiguan" (PC 6), disperse-dense wave, frequency of 2 Hz/15 Hz, intensity of 2 mA; each EA treatment last for 20 min, once a day, and 3-day treatment was given before model establishment. The EF value was evaluated by ultrasonic cardiogram; the number of macrophages in spleen and heart was measured by flow cytometry; the expression level of NLRP3 and IL-1β in myocardium was measured by Western blot. RESULTS: Compared with the control group, the EF value was decreased in the model group (<0.001), the number of macrophages in the heart and spleen was increased (<0.001), and the expression level of NLRP3 and IL-1β in the myocardium was increased (<0.001, <0.01). Compared with the model group, the EF value was increased in the EA pretreatment group (<0.01), the number of macrophages in the heart and spleen was decreased (<0.01), and the expression level of NLRP3 and IL-1β in the myocardium was decreased (<0.01, <0.05). CONCLUSION EA pretreatment could reduce the number of macrophages in spleen and heart, down-regulate the expression of NLRP3 and IL-1β in myocardial tissue in mice with acute myocardial ischemia, which could relieve the local inflammatory response and achieve the myocardial protective effect.
Acupuncture Points ; Animals ; Electroacupuncture ; Heart ; physiology ; Inflammation ; immunology ; Interleukin-1beta ; metabolism ; Macrophages ; cytology ; Male ; Mice ; Mice, Inbred C57BL ; Myocardial Ischemia ; immunology ; therapy ; Myocardium ; NLR Family, Pyrin Domain-Containing 3 Protein ; metabolism ; Random Allocation ; Spleen

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.
Animals ; C-Reactive Protein ; genetics ; immunology ; Cecum ; surgery ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Female ; Heart ; drug effects ; physiopathology ; Humans ; Interleukin-6 ; genetics ; immunology ; Ligation ; adverse effects ; Male ; Myocardium ; immunology ; Phenanthrenes ; administration & dosage ; chemistry ; Punctures ; adverse effects ; Rats ; Salvia miltiorrhiza ; chemistry ; Sepsis ; drug therapy ; etiology ; immunology ; physiopathology ; Troponin T ; genetics ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology

The cardiovascular system may be one of the target organs of both immunoglobulin G4 related and non-related systemic multifocal fibrosclerosis. We present a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis on echocardiography. For a more detailed differential diagnosis, we used multimodal imaging techniques. After surgical biopsy around the abdominal aortic area in the retroperitoneum, histological examination revealed IgG4 non-related systemic multifocal fibrosclerosis. We describe the multimodal imaging used to diagnose IgG4 non-related systemic multifocal fibrosclerosis and a positive response to steroid treatment. There have been no previous case reports of IgG4 non-related systemic multifocal fibrosclerosis with intracardiac involvement. Here, we report a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis.
Aged ; Aorta, Abdominal/pathology ; Diagnosis, Differential ; Echocardiography ; Female ; Humans ; Immunoglobulin G/*blood/immunology ; Magnetic Resonance Imaging ; Mitral Valve Stenosis/diagnosis ; Myocardium/*pathology ; Peritoneum/surgery ; Positron-Emission Tomography ; Retroperitoneal Fibrosis/*congenital/diagnosis/drug therapy/ultrasonography ; Steroids/therapeutic use ; Tomography, X-Ray Computed

The ischemic heart disease has been endangering human health seriously. Although there are many kinds of anti-ischemic drugs, most of them are lacking in tissue specificity, which together with a remarkably reduced blood circulation in the ischemic zone often lead to a quite low drug distribution in the targets. Myocardial ischemia can cause a lot of pathophysiological changes, such as the enhanced permeability of the endothelial cell membrane, the up-regulated expression of various cell adhesion molecules on endothelium, the exposure of intracellular antigenic components, the decrease of pH within the ischemic zone, and so on. To date, some of these changes have been exploited with limited success to gain the passive, active and physicochemical targeting of diagnostic or therapeutic drugs to myocardial ischemic regions. However, more effective delivery strategies are still eagerly needed. Here, we reviewed and discussed the potential targeting-delivery mechanisms and strategies, used or may be used in the future, for myocardial ischemic regions.
Animals ; Antibodies, Monoclonal ; immunology ; Capillary Permeability ; Drug Carriers ; Drug Delivery Systems ; methods ; Genetic Therapy ; Humans ; Liposomes ; chemistry ; metabolism ; Myocardial Ischemia ; therapy ; Myocardium ; metabolism ; pathology ; Polyethylene Glycols ; metabolism ; Ultrasonics

OBJECTIVETo study the effect of Extractum trametes robiniophila murr on cardiac allograft rejection in mice.

METHODSAll abdominal heterotopic heart transplantation models were divided into three groups as follows: (A) Extractum trametes robiniophila murr group. (B) Rejection group. (C) Isograft group. In each group, mean survival times (MST) of transplanted hearts and their pathologic histological changes at postoperative fifth day were observed. With fluoroimmunoassay, granzyme B and CD8(+) expressions were examined.

RESULTSThe MST of heart allografts in group A were (6.38 +/- 0.69) d, significantly shorter than that of group B [(8.31 +/- 0.59) d] (P < 0.01). In group A, acute rejection was present in advance; transplanted hearts were seriously damaged into acute rejection pathological grade 3, and CD8(+) T lymphocytes infiltrated diffusely and the expression of granzyme B increased significantly as compared with other groups.

CONCLUSIONSExclusive application of Extractum trametes robiniophila murr can promote the acute rejection of graft in early phase of postoperation, and the mechanism may be the promoted proliferation and infiltration of CD8(+) T lymphocytes and the increased expression of granzyme B.

Animals ; CD8-Positive T-Lymphocytes ; immunology ; Drugs, Chinese Herbal ; adverse effects ; Female ; Graft Rejection ; chemically induced ; Granzymes ; metabolism ; Heart Transplantation ; Male ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Myocardium ; enzymology ; immunology ; Postoperative Care

OBJECTIVETo explore the action mechanism of the immune active components of sappon wood (SWE) for antagonizing reject reaction by observing the influence of its ethyl acetate extract on mRNA expression of myocardial GrB in rat model of allogenic ectopic cardiac transplantation.

METHODSAnimal model of abdominal cardiac ectopic transplantation was established taking Wistar rat as the donor and SD rat as the receptor. The successfully modeled rats were randomly divided into the model group, the SWE group and the CsA group. GrB mRNA expression was detected by RT-PCR method and myocardial pathomorphologic picture was observed in routine.

RESULTSThe pathologic changes in the SWE group (23 scores) and the CsA group (14 scores) were milder than in the model group (31 scores), the former two could markedly alleviate the myocardial pathologic injury (P<0.05, P<0.01). The GrB mRNA expression in the model group was 1.3000 +/- 0.1207, the SWE group 0. 7070 +/- 0.1215, and the CsA group 0.6700 +/- 0.0997, respectively; compared with the model group, the latter two could obviously down-regulate the expression of GrB mRNA (P<0.01) and no significant difference was found between the latter two groups (P>0.05).

CONCLUSIONSWE could alleviate the pathologic change, down-regulate the mRNA expression of myocardial GrB in allogenic ectopic transplanted myocardium of rats, it is possibly one of the factors for its antagonizing effect against reject reaction.

Acetates ; chemistry ; Animals ; Caesalpinia ; chemistry ; Gene Expression Regulation, Enzymologic ; drug effects ; Graft Rejection ; drug therapy ; Granzymes ; genetics ; Heart ; drug effects ; Heart Transplantation ; immunology ; Male ; Models, Animal ; Myocardium ; metabolism ; pathology ; Plant Extracts ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Rats ; Transplantation, Homologous

OBJECTIVETo investigate the effect of ginkgo biloba extract (ginaton) preconditioning on discordant cardiac xenografts from guinea pig to rat, and explore its mechanism.

METHODSCervical cardiac transplantation model was established in the rats,which were divided into 4 groups Group 1 (cobra venom factor ( CVF) pretreatment, n = 10]; Group 2 (CVF + ginaton, n = 5) ; Group 3 Ccyclosporine (CsA); Group 4 (CVF + CsA + ginaton, n = 8]. The survival time and histopathology after xenograft were observed and expressions of intercellular adhesion molecule-1 (ICAM-1) heme oxygenase-1 (HO-1) CD68 and CD57 were detected.

RESULTSPathologic manifestion of grafts showed changes of acute vascular rejection (AVR) in all groups. The mean survival time after car diac xenograft was 41 hrs in Group 1, 68 hrs in Group 2, 55 hrs in Group 3 and 74 hrs in Group 4. Expression of intercellular adhesion molecule-1 (ICAM-1 ) decreased after ginaton preconditioning (P < 0. 05). CD68 and CD57 expressions were down-regulated, HO-1 expression was up-regulated, as well as the apoptotic index (Al) reduced significantly after ginaton with cyclosporine A preconditioning.

CONCLUSIONGinaton preconditioning can prolong the survival time after discordant xenograft, and significantly alleviate pathological lesion from acute xenograft vascular rejection combined with cyclosporine A.

Animals ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; CD57 Antigens ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Ginkgo biloba ; Guinea Pigs ; Heart ; drug effects ; Heart Transplantation ; Heme Oxygenase-1 ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Myocardium ; immunology ; metabolism ; Rats ; Transplantation Conditioning ; Transplantation, Heterologous

OBJECTIVETo investigate the role of immunodeficiency and intestinal mixed infection on inducing extraintestinal dissemination of rotavirus (RV).

METHODSImmunodeficiency was induced in healthy Kunming mice by introperitoneal injection of cyclophosphamide, and RV was administered either orally or via intraperitoneal injection. In another group, toxigenic E. coli and human RV were given sequentially by intragastric administration to induce mixed infection. Three days later the organs of the mice were taken for pathological examination, and RV was detected by in situ PCR and hybridization. In children with or without viremia of rotavirus, blood tests for levels of tumor necrosis factor alpha (TNF-alpha), interleukin-2 (IL-2) and 7 trace elements (zinc, iron, copper, lead, calcium, manganese, and magnesium) were performed.

RESULTSIn immunodeficient mice, pathological changes were found in the small intestinal villus, gastric lamina propria and the cardiac cells of mice taking RV orally, and the mice with intraperitoneal RV injection showed additional liver and kidney pathologies. In mice with mixed infections, pathological changes occurred in the intestines, livers and kidneys. In situ hybridization detected RV in the intestinal villus of immunodeficient mice with oral RV administration, and in the intestinal villus and kidneys of the mice with mixed infections. In situ PCR revealed the presence of RV in the intestinal villus, intestinal gland cells, epithelial cells of the proximal convoluted tubules and collecting tubes in the kidneys of immunodeficient mice taking RV orally, in the intestinal villus, kidneys, livers, hearts and pancreases of those with RV injection, and in the intestines, kidneys, and livers of the mice with mixed infection. Children with rotavirus viremia had TNF-alpha level in comparison with those free of rotavirus viremia, and the majority of the former children showed disorder in trace elements.

CONCLUSIONImmunodeficiency, mixed infection and malnutrition can be important factors contributing to or exacerbating RV infection and extraintestinal RV dissemination.

Animals ; Cyclophosphamide ; administration & dosage ; toxicity ; DNA, Viral ; genetics ; Enzyme-Linked Immunosorbent Assay ; Female ; Immunocompromised Host ; drug effects ; immunology ; Interleukin-2 ; blood ; Intestines ; pathology ; virology ; Kidney ; pathology ; virology ; Liver ; pathology ; virology ; Male ; Mice ; Myocardium ; pathology ; Polymerase Chain Reaction ; Rotavirus ; genetics ; immunology ; Rotavirus Infections ; blood ; immunology ; virology ; Trace Elements ; blood ; Tumor Necrosis Factor-alpha ; blood

The hypertension is one of chronic vascular diseases, which often implicates multiple tissues causing stroke, cardiac hypertrophy, and renal failure. A growing body of evidence suggests that inflammatory mechanisms are important participants in the pathophysiology of hypertension. In this study, the inflammatory status of these tissues (kidney, liver, heart, and brain) in spontaneously hypertensive rats (SHR) was analyzed and its molecular mechanism was explored. The tissues were dissected from SHR and age-matched control Wistar-Kyoto (WKY) rats to investigate the abundance of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma). mRNA levels were determined by reverse transcription-polymerase chain reaction and protein expression was evaluated by Western blot. To evaluate the oxidative stress of tissues, carbonyl protein content and total antioxidant capacity of tissues were detected by spectrophotometry and ferric reduction ability power (FRAP) method. The results suggest that: (1) Expressions of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma) in SHR were higher compared with those in WKY rats except no evident increase of IL-1beta mRNA in liver and brain in SHR. (2) Tissues in SHR contained obviously increased carbonyl protein (nmol/mg protein) compared to that in WKY rats (8.93+/-1.08 vs 2.27+/-0.43 for kidney, 2.23+/-0.23 vs 0.17+/-0.02 for heart, 13.42+/-1.10 vs 5.72+/-1.01 for brain, respectively, P<0.05). However, no evident difference in the amount of carbonyl protein in liver was detected between SHR and WKY rats. (3) Total antioxidant capacities of kidney, liver, heart and brain were markedly lower in SHR than that in WKY rats (P<0.05). Thus, the present data reveal a higher inflammatory status in the important tissues in SHR and indicate that inflammation might play a potential role in pathogenesis of hypertension and secondary organ complications.
Animals ; Brain ; metabolism ; pathology ; Cytokines ; genetics ; metabolism ; Hypertension ; pathology ; Inflammation ; pathology ; Interleukin-1beta ; genetics ; metabolism ; Kidney ; metabolism ; pathology ; Male ; Myocardium ; metabolism ; pathology ; Oxidative Stress ; immunology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Tumor Necrosis Factor-alpha ; genetics ; metabolism