A new study published in the journal Circulation Research is perhaps the first to show changes of the innate cells network and traffic in ischemic heart failure.
Heart failure (HF) remains a major health issue, and evidence accumulated over the last decade has established immune activation or inflammation as a major pathogenic factor in chronic HF.
However, anti- inflammatory strategies have produced modest results or no therapeutic benefit and to date, no large-scale immunomodulatory therapies have been successfully translated to clinical practice. This also includes clinical trials targeting inflammatory mediators such as tumor necrosis factor (TNF)-α, a major pro-inflammatory ‘hormone’ or cytokine (cf. U. Hofmann & Frantz S., Basic Res Cardiol, 2013; 108:356).
So far, the main research focus in HF has been directed toward pro-inflammatory mediators such as cytokines.
Lesser attention has been given to the role of immune and inflammatory cell networks in this condition. It is known that in acute myocardial infarction, monocytes and dendritic cells (DCs) are involved in early post-infarction remodeling.
Whether and how the myelomonocytic network between lymphoid tissue and the heart is altered in chronic HF still remains undefined.
Now the study by Mohamed Ismahil and colleagues, from the Department of Medicine, University of Alabama at Birmingham VAMC, Birmingham, AL in Circulation Research demonstrates extreme changes of the mononuclear phagocyte network in ischemic HF that include the failing heart, spleen, peripheral blood, and bone marrow. Moreover, it shows that mononuclear splenocytes in chronic HF are highly activated and traffic to the heart to induce immune cell-mediated injury.
The authors suggest that activation of innate immune cells may represent a major pathogenic mechanism in HF, where the splenic microenvironment may play a major role. According to the authors the progression of pathological cardiac remodeling is presumably and partially dependent on autoimmune heart damage induced by activated mononuclear phagocytes.
Source: Circ Res, 2014, 114:266. doi: 10.1161/CIRCRESAHA.113.301720. Epub 2013 Nov 1.
Read More: Circulation Research