Even though I have been studying immunology for 15 years, I am constantly fascinated by how elaborately involved the immune system is in different diseases and conditions. I have written previously about the intricate relationship between the immune system and heart disease. In this blog, I will be highlighting the role of the immune system in hypertension, focusing on a new study that examined the role of complements and regulatory T cells in hypertension.
According to the CDC, there are 75 million people – a third of the population – in the USA with hypertension. Another third of the population is at risk, being at a pre-hypertensive state. With the change in blood pressure guidelines that was announced at the end of 2017, it is expected that the number of people affected with hypertension will increase substantially. While half of the patients with hypertension have their high blood pressure under control, hypertension still contributes to more than 1,000 deaths per day in the US.
It is evident that the immune system is involved during hypertension. Activated immune cells can infiltrate target organs such as the perivascular tissue and the kidneys. Macrophages, an innate immune and phagocytic cell, contribute to hypertension by increasing inflammation and oxidative burst. T cells, a key adaptive immune cell, can also be found infiltrating aortas, perivascular tissue, vascular vessels as well as the kidneys, where they can produce inflammatory mediators. The lack of the above two cell types has been shown to reduce blood pressure in angiotensin II infusion mouse models.
A recent study in Circulation Research examined how the complement system affected regulatory T cells during hypertension. The authors show that two complement receptors, C3aR and C5aR, are increased on regulatory T cells, an anti-inflammatory T cells that protects against heart disease. The increase in complement receptors led to a reduction of the protective regulatory T cells in hypertensive mice. By deleting the two complement receptors, the authors show that there is a decrease in systolic and diastolic blood pressure and regulatory T cells were preserved in the angiotensin II treated mice. The authors also show that similar increase in C5aR is found in patients with hypertension.
Complements are a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells, having beneficial effects in immune defense. It is already known that ischemia is a potent activator of the complement system and the activated complement system play a role in tissue damage during myocardial infarction and contribute to atherosclerosis progression. There are studies to show that inhibition of the complement system can reduce myocardial infarction. Can the inhibition of the complement system assist in hypertension reduction in patients? Would scientists be able to design therapies that limit the activation of the complement system to benefit hypertensive patients without complete abrogation of the complements anti-microbial properties? There are still many uncertainties about how the scientific community can manipulate the complement system to benefit patients with hypertension, but I think the more advances we make in understanding how the different players in the immune system affect hypertension and other heart related conditions, the better we fair in getting closer to new therapies against heart disease.
Dalia Gaddis is a postdoctoral fellow at the La Jolla Institute for Allergy and Immunology. She has a Ph.D. in microbiology and immunology. She is currently working on understanding the interactions between the immune system and atherosclerosis development.