The Answer:

In addition to the high morbidity and mortality associated with myocardial infarction, one of the major challenges in cardiovascular research has been reconciling the varied presentation of cardiac disease in patients. In this context, our goal with this project was to develop our understanding of the physiological processes at play in normal and diseased hearts by reading through scientific literature and speaking to professionals in the field (see The Interview). Ultimately, we used the knowledge we built up to discuss promising developments in diagnostic measures and therapeutic strategies for heart disease (see Figure 1). 

Figure 1. Physiology Informs Diagnostic and Therapeutic Methods. Figure created with BioRender.com

Since we initially set out to explore heart regeneration, we began by looking into physiology from a regenerative perspective. By understanding the Regulators of Cardiomyocyte Proliferation and Cardiomyocyte Differentiation from Stem Cells and the interplay between proliferation and differentiation, we were able to contextualize some physiological hurdles being faced in regenerative research and how they can be overcome. Most notably, cardiac cells have several regulatory pathways in place which prevent them from regaining their proliferative capacity and ability to differentiate. With that being said, some pathways involved in cardiomyocyte proliferation can, if targeted early, increase the regenerative capacity of the heart. This approach relates directly to the engineering of cardiomyocytes from human induced pluripotent stem cells (hiPSCs), which has therapeutic relevance – see Paper 1.

Our interest in diagnostic methods stemmed from the ambiguity of cardiac disease-related symptoms. As such, we explored several modalities of Molecular Imaging designed to detect and characterize heart disease based on biochemical activity. Gene Expression Markers were also of interest to us given that this project was deeply rooted in processes occurring at a molecular level; genomic and transcriptomic characterization of heart disease has important diagnostic and prognostic relevance. Finally, we explored Troponin Protein Concentration as a diagnostic marker for cardiac injury given the mechanistic importance of the troponin complex in cardiac contraction.

We found two major biomaterial-based therapeutic approaches for heart regeneration that function by attempting to replicate cardiac anatomy and physiology. Fibrin Glue-Based Cardiac Patches and Hydrogels involve grafting engineered material onto injured hearts to mimic healthy cardiac tissue and restore function. The experimental methods that we explored for these strategies helped contextualize the types of techniques (i.e. animal models, electrochemical assays, staining, etc.) used in the field of biomaterial-based cardiac regeneration and the general direction of research in the field – see Paper 2 and Paper 3.

This project gave us an appreciation for the relationship between physiology and pathology. We hope that there continues to be an emphasis on understanding the physiological basis of heart disease so that diagnostic and therapeutic methods can apply to a wider array of patients across the globe.

73 Comments

  1. Katerina V. Varsamis

    December 7, 2023 at 8:48 pm

    I really like your usage of links to other parts of your webpage; it helps me clearly see how specific parts of the website connect to one another and offers the reader with a very clear roadmap of how to approach all the information included in the website.

    Here, figure 1 is not referred to explicitly at any point in the text, so I was unclear on when the best moment to refer to it was. Maybe include a parenthetical mention to it “(Figure 1)” at the end of the first paragraph (I am assuming that the last sentence of that paragraph is what the figure is depicting based on the caption).

  2. Joaquin T. de Jesus

    December 8, 2023 at 2:19 pm

    I’m quite impressed with the breadth of your research for this project. It’s interesting to see how the regeneration and proliferation are regulated. Though I’m a bit confused as my understanding of CVD led me to think that it was more so a result of stress applied to the heart due arterial plaques or difficulty with circulation. In those cases, I would find it difficult to see how some of the therapies being used would help in those cases. Rather, I would have thought that these therapies would be appropriate for acute injury or trauma to the heart. Are the treatments targeting strained or sites of deterioration in the heart as a result of disease? Overall it’s really interesting seeing all of these concepts coming together.

  3. I love how your figure 1 breaks down the macro to molecular in a easy and accessible way.

    “This type of approach has specific relevance to the engineering cardiomyocytes from human induced pluripotent stem cells (hiPSCs) that can have therapeutic relevance – see Paper 1” this sentence is a bit awkward, I would restructure it.

  4. I think your answer for your question 1 should be direct and more fleshed out like your answer to question 2 which is very clear. I understand that it is a more difficult question to answer concisely but if it is to be addressed anywhere in your site, it should be on the answer page.

  5. Came back to this page last after reading all the others and I can definitely see the big picture! Really great work with this project guys and I appreciate all the links on this page. You tie everything together well, all I would like to see at this point is more of your group’s opinion (based on everything explored) on where the field is going in the future, what therapies seem most effective to you, and where future studies might lie. Good work!

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