Tag Archives: oxidative stress

Heart Health: Slowing the Progression of Heart Failure
Amal Altaf
Junior
Biological sciences (BS) and global health (BA)
Barrett at Arizona State University

My Research Project

Cardiac fibroblasts are cells in the heart that are involved in producing proteins such as collagen. An accumulation of these proteins leads to a medical diagnosis termed fibrosis, which plays a major role in the progression of heart failure. Proteins such as angiotensin II are known to activate fibroblasts and promote fibrosis. Reactive oxygen species (ROS) are unstable molecules in the cell that have been suspected to play a role in angiotensin-II-induced inflammation and, consequently, fibrosis. An imbalance of ROS in the cells is called oxidative stress. While no treatment is known to reverse fibrosis, a class of drugs known as angiotensin converting enzyme inhibitors (ACEI) are able to slow its progression, even after ACEI treatment has been stopped. However, it is unknown how ACEI treatment is able to protect against fibrosis.

In this experiment, I was tasked with investigating whether the protection against fibrosis was a consequence of a more favorable oxidative stress profile in response to angiotensin II treatment. Using heart tissue from the left ventricle of rats my lab was able to test our hypotheses. The rats were divided into three treatment groups, each treated for a total of six weeks, The treatment proposed on the rat models is depicted by the table below.

Because ACEI has been previously shown to protect against fibrosis, we hypothesized that hearts from hypertensive rats previously treated with ACEI would show decreased protein expression of pro- and anti-oxidant enzymes in response to angiotensin II, which corresponds to Group 3 in the table above. Understanding whether oxidative stress is altered due to prior ACEI treatment will allow for a better understanding of the mechanisms through which the heart can become more resistant to fibrosis. This may contribute to a better understanding of cardiac fibrosis and the development of novel treatments that may slow or prevent heart failure.

Realities of Research

Loading of Western Blot gel.

It surprised me, but I quickly learned that research involved a great deal of trial and error. I learned that while every step in the research plan is well thought out, there is still a lot of uncertainty. However, that was not a bad thing, because that uncertainty is exactly what we are targeting through our research. We sought to understand things we did not already know. My experience this summer forced me to learn new techniques, such as those of western blotting, imaging via film, and technology and analysis. I was also been fortunate enough to shadow others in the lab and gain better understanding of several other procedures such as surgeries, cell culture and immunohistochemistry.

More often than not, the results I received were different from what I expected, which led to several discussions with my research host about possible explanations and potential next steps, very often being revised. It almost reminded me of the game “Chutes and Ladders.” We would make progress in the direction we expected, then come across unexpected results which sometimes brought us back to square one or took us in a new direction. I’m not entirely sure how many times we had to start over, but we certainly had to go back and change our plan several times. We actually just revised our research question a few weeks prior to wrapping up the summer research!

Life as a Scientist

The daily life of a scientist is much more than mixing chemicals and making graphs. My life as a scientist this summer provided me with insight into the reality of working in a research lab. Beyond the trial and error, the uncertainty and the constant learning that all made each day in this field so intriguing, there was also a great amount of collaboration involved. Working as part of a team was one of my favorite parts of being a scientist. I worked towards a common goal with my lab team, but also worked with people outside of my lab, even those whose research had a different focus. My least favorite part of working in the lab was how writing-intensive it was.

When picturing a scientist, a person in a lab coat working at a lab bench usually comes to mind. In reality, the life of a scientist involves a considerable amount of writing in order to obtain grants to fund the research and to communicate the research. While this hasn’t been completely applicable to my case (since I’m not writing grants—yet!), I would still consider it to be the “worst” part about the day-to-day life of a scientist. All in all, my time in the lab this summer allowed me to gain an invaluable understanding not only of the research project I worked on, but also the realities of research and the life of a scientist.

Amal Altaf is a junior double majoring in biological sciences and global health at Barrett, The Honors College at Arizona State University in Tempe, Ariz. She is a 2019 Undergraduate Summer Research Fellow (UGSRF) working in Dr. Taben Hale’s lab at the University of Arizona College of Medicine in Phoenix. Amal’s fellowship is funded by the American Physiological Society. Upon graduating, Amal hopes to pursue medical school to eventually practice as a physician

My Summer of Science

In the summer of 2017 I spent my time working an unconventional full-time job in the lab growing as a scientist. I was given an opportunity to be mentored by an established research professor who I look up to greatly. She helped me step by step go through the process of coming up with a project, understanding the current research in the field, and guiding me through the behind the scenes documentation to get fully approved by local, state, and federal agencies.

My project that I am undertaking is geared towards ultimately understanding the roll of dietary choices and its implications on oxidative stress, leading to potential for cardiovascular disease. My lab and I are utilizing birds as a model to demonstrate the effects of a high-carbohydrate diet and its ability to cause a hyperglycemic condition. For the study, Mourning Doves will be used due to their high density in the Tempe, AZ area and much of the studies leading up to this used the same birds. They have a unique ability to combat the oxidative stress that is commonly seen due to high blood sugar. We hope to better understand how their body combats the negative effects of hyperglycemia in efforts to process the information regarding the protective mechanisms of the vascular system.

Realities of Research

The idea of moving research forward can be very attractive. The actual process of progressing it may not be as attractive. Research is a very meticulous, detail-oriented task that needs to be well planned, documented, and thought-out for it to properly work. There is no book you can read that gives you the exact answer to what you are doing. This is the world of the unknown and if properly done could potentially help shift the understanding for those to come after you. However, a major hiccup that I believe is frequently over looked as a young scientist going into a research lab is that it’s quite common to get negative results, or even though the data seems to support what you thought, it is not statistically valid based on the mathematical analysis. This is a huge part of research and can be very testing of resiliency as the process of getting this far could take months or years.

Life of a Scientist

Although, it is common to see science hitting the news headlines frequently on your phone and social media feed, it is a much longer process of meticulous work than what is publicized. In the efforts of using an animal in the aide of progressing the scientific community there is a very stringent process of approvals needed to work with them. For example, Mourning Doves are migratory birds, so my project requires an approval by the Arizona State Game and Fish Department, the U.S. Fish and Wildlife services, and the Institutional Animal Care and Use Committee (IACUC) before I can begin the research itself. I was surprised as I began to work in the lab by all the intricacies of administrative background work that went into being able to conduct research. While repeating experiments take a lot of time and effort, I now feel as if there is equal if not more effort done in paperwork and formalities than physical experimentation. I, myself am still waiting to begin the physical hands on portion of the research. I have worked through the course of the summer gaining valuable experience in the creation of the protocol and understanding the approval process. I have also been given the opportunity this summer to work very closely with another research project that is much larger than my own.

This summer has been an invaluable experience in research that I would not have gained otherwise without the gracious efforts of the APS.

References

  1. Braun, and Sweazea. “Glucose Regulation in Birds.” Comparative Biochemistry and Physiology, Part B1 (2008): 1-9. Web.
  2. Smith, Toomey, Walker, Braun, Wolf, Mcgraw, and Sweazea. “Naturally High Plasma Glucose Levels in Mourning Doves ( Zenaida Macroura) Do Not Lead to High Levels of Reactive Oxygen Species in the Vasculature.” Zoology3 (2011): 171-76. Web.
  3. Sweazea, Braun, and Sparr. “Novel Role of Insulin in the Regulation of Glucose Excretion by Mourning Doves (Zenaida Macroura).” Zoology122 (2017): 58-62. Web.
Will Clark is a senior biochemistry student at Arizona State University in Tempe, AZ. He is a 2017 Integrative Organismal Systems Physiology (IOSP) fellow conducting research in the lab of Dr. Karen Sweazea at Arizona State University. His long-term goal is to become a Physicians Assistant, and join the health care workforce to help improve the health and well-being of others.