T Lymphocytes and Anticardiac Antibodies in Patients with Ischemic Heart Diseases

Agrawal, Chandra G.; Gupta, Swami P.; Chaturvedi, U. C.; Mitra, M.K.; Gupta, Nitya N.; Gupta, Sudhir

doi:10.1159/000232109

Cited by 9 publications

(2 citation statements)

References 15 publications

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“…[15][16][17][18][19] For example, anticardiac antibodies and sensitized T lymphocytes have been detected in patients with acute MI. 20 Lymphocytes have also been implicated in cardiomyocyte injury during autoimmune myocarditis, [21][22][23][24][25] and spontaneous RAG2-dependent, lymphocyte-mediated immune responses in mice lacking the negative immunoregulatory receptor PD-1 cause dilated cardiomyopathy and death from congestive heart failure. 26 Here we established the presence of T cells in the hearts of dKO mice.…”

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confidence: 99%

Lymphocytes Are Not Required for the Rapid Onset of Coronary Heart Disease in Scavenger Receptor Class B Type I/Apolipoprotein E Double Knockout Mice

Karackattu

Picard

Krieger

2005

ATVB

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Objective-Scavenger receptor class B type I (SR-BI)/apolipoprotein E (apoE) double knockout (dKO) mice exhibit many features of human coronary heart disease (CHD), including occlusive coronary atherosclerosis, cardiac hypertrophy, myocardial infarctions, and premature death. Here we determined the influence of B and T lymphocytes, which can contribute to atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte death, on pathology in dKO mice. Method and Results-The lymphocyte-deficient SR-BI/apoE/recombination activating gene 2 (RAG2) triple knockout mice and corresponding dKO controls generated for this study exhibited essentially identical lipid-rich coronary occlusions, myocardial infarctions, cardiac dysfunction, and premature death (average lifespans 41.6Ϯ0.6 and 42.0Ϯ0.5 days, respectively). Conclusions-B and T lymphocytes and associated immunoglobulin-mediated inflammation are not essential for the development and progression of CHD in dKO mice. Strikingly, the dKO mice bred for this study (mixed C57BL/6ϫSV129ϫBALB/c background; strain 2) compared with the previously described dKO mice (75:25 C57BL/6:SV129 background; strain 1) had a shorter mean lifespan and steeper survival curve, characteristics especially attractive for studying the effects of environmental, pharmacological, and genetic manipulations on cardiac pathophysiology. Key Words: atherosclerosis Ⅲ HDL receptor Ⅲ myocardial infarction Ⅲ RAG2 Ⅲ echocardiography M urine models of dyslipidemia, such as the apolipoprotein E (apoE) or low-density lipoprotein (LDL) receptor knockout (KO) mice, have been used extensively to study atherosclerosis. However, even when subjected to high-fat/highcholesterol diets, all but one of these hypercholesterolemia and atherosclerosis systems usually do not result in spontaneous development of occlusive coronary artery disease, myocardial infarction (MI), cardiac dysfunction, or the premature death that are hallmarks of human coronary heart disease (CHD). The exception, mice doubly deficient for the HDL receptor scavenger receptor class B type I (SR-BI) and apoE (double KO [dKO]) not only exhibit extensive aortic sinus and occlusive coronary arterial atherosclerosis (advanced plaques with fibrous caps, fibrin deposition, and cholesterol clefts), but they also experience severe CHD at a very young age (4 to 6 weeks). [1][2][3] The hearts of dKO mice are hypertrophic and exhibit left ventricular (LV) dilation and multiple, large MIs. Severe cardiac dysfunction is demonstrated by multiple ECG abnormalities (ST segment elevation and depression, anesthesia-induced conductance abnormalities [eg, bradyarrhythmias, atrioventricular blocks]), a 70% reduction in ϮdP/dT, and 50% reduced ejection fraction. The mice die between 5 and 8 weeks of age (mean 6 weeks). Thus, the many similarities in CHD of dKO mice and humans raised the possibility that these mice may help in the study of the pathophysiology of CHD and genetic, pharmacological, and environmental approaches for its prevention and treatment.B and T lymphocytes ...

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Lymphocytes Are Not Required for the Rapid Onset of Coronary Heart Disease in Scavenger Receptor Class B Type I/Apolipoprotein E Double Knockout Mice

Karackattu

Picard

Krieger

2005

ATVB

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“…[7][8][9][10][11] In several models of autoimmune disease, including a rat model of myocarditis, transfer of splenic lymphocytes sensitized to an offending antigen into syngeneic rats led to adoptive transfer of the disease. [12][13][14][15][16][17][18] This technique of "adoptive transfer" into syngeneic rats enables us to distinguish ischemiarelated injury from the subsequent immune-mediated injury.…”

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Experimental Autoimmune Myocarditis Produced by Adoptive Transfer of Splenocytes After Myocardial Infarction

Maisel

Cesario

Baird

et al. 1998

Circulation Research

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One possible mechanism for neurohumoral activation after myocardial infarction may be the generation of an immune response against cardiac self-antigens. We hypothesize that if there is a T cell-mediated reaction to self-antigens, the transfer of splenic lymphocytes from postinfarct rats into syngeneic rats with normal hearts should result in a T cell-mediated autoimmune myocarditis in the healthy syngeneic rats. Rats were killed 6 weeks after coronary ligation. Splenocytes from animals with large and small infarcts were purified from spleens, activated with concanavalin A, and injected in varying doses into normal syngeneic rats. These recipient rats were killed 6 weeks later, and histopathological studies were performed. Our results demonstrate in vivo evidence of lymphocyte-mediated myocardial injury by adoptive transfer of sensitized lymphocytes from rats who developed congestive heart failure after acute myocardial infarction. The amount of infiltrate and necrosis in the recipient rats appeared directly related to the size of the infarct from the donor rats. This suggests that larger infarcts lead to a greater inflammatory response as well as a greater propensity for alteration of cardiac surface antigens or the emergence of previously sequestered antigens. None of the other organs (kidney, liver, lung, or brain) had evidence of infiltrates. Two-dimensional echocardiography did not reveal systolic dysfunction. This study provides direct evidence of autoimmune myocardial injury produced by adoptive transfer of concanavalin A-activated splenocytes after myocardial infarction. We propose that neurohumoral activation early in the postinfarction period triggers a series of specific inflammatory and immunological events that lead to formation of specific clones of T cells. When these are activated and transferred into normal rats, cardiac-specific cellular infiltration occurs, occasionally accompanied by myocardial necrosis. This model should help to further explore the link between neurohumoral activation after myocardial infarction and the subsequent immune alterations that might be associated with the development and/or progression of congestive heart failure. Additionally, this might be a useful model in which to study other immune-mediated cardiomyopathies.

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Dilated (Congestive) Cardiomyopathy—The evidence for and Against a Disorder of Cellular Immunity and Infection

Lowry¹,

Littler²,

Bolte³

1985

Heart Muscle Disease

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T Lymphocytes and Anticardiac Antibodies in Patients with Ischemic Heart Diseases

Cited by 9 publications

References 15 publications

Lymphocytes Are Not Required for the Rapid Onset of Coronary Heart Disease in Scavenger Receptor Class B Type I/Apolipoprotein E Double Knockout Mice

Lymphocytes Are Not Required for the Rapid Onset of Coronary Heart Disease in Scavenger Receptor Class B Type I/Apolipoprotein E Double Knockout Mice

Experimental Autoimmune Myocarditis Produced by Adoptive Transfer of Splenocytes After Myocardial Infarction

Dilated (Congestive) Cardiomyopathy—The evidence for and Against a Disorder of Cellular Immunity and Infection

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