Part 3 of 3: The Hypertension Series

In the first two parts of our hypertension blog series, we explored how genetic and particulate matter (PM) influences hypertension separately. But here’s a thought: could particulate matter influence the effects of genetics on hypertension? And what about the other direction? The answers to both of those questions appear to be a resounding “yes.” 

To begin with, let’s gain some technical mastery over the process by which DNA is converted into a protein. Your body first needs to “unlock” the genetic code stored in your DNA, which it does through a process called transcription. Essentially, a bunch of enzymes descend upon a specific location of the DNA, unzip it, and copy the gene of interest as RNA, since your body is much better at deciphering RNA than DNA.

That RNA copy is called mRNA (which stands for “messenger RNA”). mRNA is then processed further, and  eventually comes into association with one of many ribosomes, which are the major protein production factories of your cells. The ribosome translates the genetic code in the mRNA to produce a protein.

One of the first points of intersection between PM and our genes is through its interaction with DNA. There are several different ways to modify DNA, so for simplicity’s sake, we’ll be honing in on two of the big ones: DNA methylation and histone modification. 

DNA Methylation: As the name suggests, DNA methylation is the process of adding or removing methyl groups (a simple compound composed of carbon and hydrogen) from the backbone of DNA. In most cases, methylating various segments of DNA serves to silence transcription, the first stage of gene expression. Think of methylation as an on/off switch for our genes. Proper regulation of methylation is incredibly important for maintaining stable internal conditions in the body. Turning on genes when they shouldn’t be on, or turning off genes when they shouldn’t be off are both situations that are highly detrimental to our health. Therefore, research showing that  PM-related DNA hypomethylation (decreased methylation) is connected with elevated blood pressure, appears to be a matter of great concern (Bellavia et al, 2013). 

Histone Modification: Histones are proteins that aid in the packaging of DNA, thereby playing a major role in fitting the 3 billion base-pair strands into a cell’s nucleus in a compact way. A process known as histone acetylation causes the histones to lose grip over the DNA, resulting in genes becoming more accessible for transcription. In opposition, deacetylation of the histones causes the histones to wrap around DNA more tightly, which prevents gene expression. 

Specific built-in mechanisms in different cells use histone modifications to activate or deactivate genes. A recent study provides evidence that exposure to vehicular air pollution PM10 is associated with histone H3 modification in human white blood cells (Zheng et al, 2016). Another study highlighted that PM2.5 inhalation caused lung inflammation associated with histone modification. (Ji et al, 2018).

These epigenetic changes that we just looked at focus on PM’s efforts to prevent a gene from being converted or transcribed into an RNA molecule. But what if an mRNA molecule is able to form? Are there ways in which PM can prevent its translation into a protein? Let’s explore that next!

RNA Silencing: An important epigenetic tool the body uses for changing gene expression is something called micro RNA (miRNA). miRNA are very, very small pieces of RNA –  which is really saying something since regular RNA itself is nanoscopic. 

miRNA associates itself with a protein complex which eventually binds to the mRNA and tags it for destruction, thereby thwarting gene expression. This is an important regulatory feature, since it can degrade wrongly transcribed RNA molecules. 

However, research suggests that inhaled particulate matter might affect miRNA levels in the body. With respect to blood pressure, levels of miRNA implicated in blood pressure maintenance processes were shown to be decreased (Motta et al, 2016). This, in conjunction with particulate matter effects on DNA methylation and histone modification, provide evidence that disrupted regulation of gene expression may be of interest when considering the forces at play driving blood pressure abnormalities.

Skeletal Muscle SNPs: Due to the vast amount of genetic variability from person to person, PM can have differing degrees of effects. Consider our skeletal muscle cells, which rapidly contract and expand to create all of our voluntary bodily movements. The contractive forces are a result of chemical processes, which create a lot of waste byproducts such as reactive oxygen species, chloride, potassium, lactic acid, ADP, magnesium (Mg 2+) and inorganic phosphate molecules. We all have receptors in our skeletal muscle nerves that can detect such chemical stimuli and send signals to our brain, causing an increase in blood flow and pressure to eliminate the byproducts. However, some of us might have SNPs (specific genetic mutations) that make us overly sensitive to any chemical stimuli. The increase in PM (a chemical stimuli), can lead to hypertension in these individuals at a faster pace than individuals lacking such an SNP. 

There are myriad examples of SNPs dictating the effects of PM, which are waiting to be understood at a deeper level. The daunting task of digging deep into the literature to make sense of the relationships between the different variables is the biggest barrier standing between our status quo and the future of medicine. This means that hope lies in the cooperation between health innovators, physicians and policy-makers to tackle these data-based challenges to usher in a new era of medicine.

 

References

Bellavia, A., Urch, B., Speck, M., Brook, R. D., Scott, J. A., Albetti, B., . . . Baccarelli, A. A. (2013). DNA Hypomethylation, Ambient Particulate Matter, and Increased Blood Pressure: Findings From Controlled Human Exposure Experiments. Journal of the American Heart Association, 2(3). doi:10.1161/jaha.113.000212

Ji, X., Yue, H., Ku, T., Zhang, Y., Yun, Y., Li, G., & Sang, N. (2019). Histone modification in the lung injury and recovery of mice in response to PM2.5 exposure. Chemosphere,220, 127-136. doi:10.1016/j.chemosphere.2018.12.079

Motta, V., Favero, C., Dioni, L., Iodice, S., Battaglia, C., Angelici, L., . . . Bollati, V. (2016). MicroRNAs are associated with blood-pressure effects of exposure to particulate matter: Results from a mediated moderation analysis. Environmental Research, 146, 274-281. doi:10.1016/j.envres.2016.01.010

Zheng, Y., Sanchez-Guerra, M., Zhang, Z., Joyce, B. T., Zhong, J., Kresovich, J. K., . . . Hou, L. (2017). Traffic-derived particulate matter exposure and histone H3 modification: A repeated measures study. Environmental Research, 153, 112-119. doi:10.1016/j.envres.2016.11.015