Nishi Jain 21′
The aggregation of macrophages within cardiac tissue and arteries are a consequence of atherosclerosis (buildup of plaque in the blood vessels). Imaging like this, in addition to the frequently used angiogram, can help diagnose atherosclerosis. (Source: Wikimedia Commons)
Heart disease has emerged as one of the most pressing and dangerous health crises of the 21st century, especially in the United States. It has quickly become one of the most prolific killers, and is (until now) only resolved by two dangerous surgeries – either a stent is placed in the affected arteries of the patient (the inflation of the stent expands the arteries and allows for greater blood flow) or bypass surgery is performed. Bypass surgery is exactly as it sounds – arteries or veins from other locations in the body are used to circumvent blood flow around the plaque that has gathered in the heart. Yet even if either surgery is successful, there is always the added danger of clots traveling elsewhere in the body – the resulting pulmonary embolisms and strokes that frequently appear after the surgery can be fatal.1
The thing that both procedures have in common is that they do nothing to reduce the size of the plaque – they only evade it (either by the ballooning of a stent or through implanted arteries that allow blood to flow around the plaque and prevent lack of oxygen to the heart). There are currently no surgical treatments that can remove a plaque entirely from the heart for fear that the plaque may dislodge and implant elsewhere in the body.1 But scientists at Albany Medical College have developed one – creating nanotubes that are capable of clearing plaques.2
Plaques within the walls of blood vessels are characterized by dense necrotic tissue cores (dead cell buildup) that are shown to have malfunctioning efferocytosis processes. Efferocytosis is the process by which phagocytic cells remove dead or dying cells. When efferocytosis is defective, the continual buildup of dead cells in the middle of arterial blood vessels obstructs blood flow to and from the heart.3 By targeting the defective efferocytosis process and remedying its problems, the body may have a shot at remedying the plaque buildup.2
The process of boosting efferocytosis is therapeutically possible. It can be done by limiting cleavage of efferocytosis receptor MerTK and masking the CD47 signals that communicate survival to the phagocytic cells. The latter of these treatments has been investigated further but has frequently led to the side effect of anemia, where there are a limited number of red blood cells circulating through the body2. Keeping this in mind, scientists have built a therapy that binds to SHP1 (SH2 domain containing phosphatase 1) which serves to trigger the survival signaling pathway. The therapy consisted of a nanotube that was complexed with a SHP1 inhibitor that was preferentially taken up by macrophages. With SHP1 inhibited, the removal pathway was expressed over the survival signaling pathway and efferocytosis was promoted2.
This is a powerful new treatment, as its focus is on correcting the body’s biochemical processes rather than killing cells (as is customary with the MerTK and CD47 treatments). While anemia remains a compelling contraindication to this therapy’s use, it is certainly an improvement upon the existing surgeries, which have been shown to be both dangerous in in the operating room and in recovery.
Bibliography
[1] Fredman, G. (2020). Devouring atherosclerotic plaques. Nat. Nanotechnol. 15, 84–85. https://doi.org/10.1038/s41565-019-0599-3.
[2] Flores, A.M., Hosseini-Nassab, N., Jarr, K. et al. (2020). Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis. Nat. Nanotechnol. 15, 154–161. https://doi.org/10.1038/s41565-019-0619-3.
[3] Doran, A.C., Yurdagul, A. & Tabas, I. (2019). Efferocytosis in health and disease. Nat Rev Immunol. https://doi.org/10.1038/s41577-019-0240-6.