The role of immune checkpoints PD-1 and CTLA-4 in cardiovascular complications leading to heart failure

Figure 1. The mechanistic role played by PD-1/L1 in maintaining cardiac homeostasis and its inhibition results in immune checkpoint mediated myocarditis. Blockade of PD-1/L1 disrupts the cardiac homeostasis resulting activation of thymocytes or T-cells, which results in expression of pro-inflammatory condition leading to myocarditis.

Figure 2. The mechanistic role of played by PD-1/L1 in immune system mediated development of Atheroscelrosis. Blocking of PD-1/L1 results in activation of thymoctes or T-cells resulting in expression of cytokines like IFN-γ, ILs and TNF-α. This further stimulates the differentiation of macrophages and subsequent release of cytokines like, TNF-α and Ils, which promote the development and proliferation of atherosclerotic plaque.

Figure 3. A digrammatic representation of involvement of different checkpoints viz., PD-1/L1, CTLA-4 and LAG-3, in atherosclerosis. The immune checkpoints imparts cardio-protective role and helps in maintaining cardio-homeostasis. These immune checkpoints imparts plaque stability and reduce the proliferation of plaque by controlling inflammation. Inhibition of these checkpoints disrupts this balance and thus promoting plaque development and proliferation.

Figure 4. A digrammatic representation of involvement of different checkpoints viz., PD-1/L1, CTLA-4 and LAG-3, in myocarditis. PD-1/L1 and CTLA-4 are responsible for keeping autoimmunity in check and thus reducing cardiac inflammation. These immune checkpoints reduce lymphocyte infiltration and phagocytosis. Inhibition of these checkpoints disrupts this balance and thus resulting inflammatory conditions leading to myocarditis.

Figure 5. A digrammatic representation of involvement of different checkpoints viz., PD-1/L1, and CTLA-4 in cardiomyopathy. PD-1/L1 and CTLA-4 reduce cardiac injury and autoimmunity in check. Inhibition of these checkpoints disrupts this balance and thus resulting in cardiomyopathy.