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How do you Study Complex Cardiac Disorders Most Effectively?

Heather Brown
Tags: Successful Research Tips,


  • The heart is a complex organ developed from neural crest cell derivatives into cardiomyocytes and driven by electrical impulses to pump blood throughout the circulatory system, to deliver oxygen and nutrients, and eliminate waste.
  • Cardiac disorders occur when the heart cannot function normally due to aberrant electrical conduction, irregular chamber dynamics, or disrupted tissue homeostasis.
  • Biomarkers such as CRP, BNP, cytokines, and interleukins are essential for developing assays and diagnostic tools to advance our understanding of heart disorders and improve patient outcomes.

The "Heart" of Circulatory System: The structure and function of the cardiac organ.

For centuries, various human cultures have often portrayed the heart as a symbolic representation of love or our emotional command center. In the fourth century B.C., the Greek philosopher Aristotle introduced the concept that the heart is the center for intelligence, emotion and sensation, and is the organ most closely related to the soul. This idea was popular for hundreds of years, remaining the dominant ideology through the 12th century. As more advanced techniques and technologies to study the heart became available, our understanding of the structure and function of the heart shifted from a metaphysical understanding to a biomedical understanding. While we now recognize the heart is the organ that pumps blood from veins into arteries throughout the body to supply nutrients and oxygen, the cultural and emotional significance of the heart remains.

The human heart is a small (only about the size of your fist) yet powerful organ with complex and unique biology that keeps us alive. Consisting of four chambers, the heart accepts oxygenated blood from the lungs, which collects into the heart's left atrium. The blood is then pumped through the mitral valve into the left ventricle, through the aorta, and is delivered to the rest of the body via arteries (Figure 1 A-D). Once the blood has transferred oxygen and nutrients to the designated tissues, the deoxygenated blood travels back to the heart through a network of veins, and enters the right atrium through the superior and inferior vena cava, collecting in the right atrium Figure 1 E-G). The blood is subsequently pumped through the tricuspid valve into the right ventricle, and pumped out of the heart via the pulmonary artery to bring blood to the lungs for oxygenation (Figure 1 H-J). This blood flow is dependent on the correct structure and function of the heart. For example, the valves are critical to inhibit blood flow from flowing backward in this process, and the septum is vital for maintaining the separation between oxygenated and deoxygenated blood (Figure 1 K). Further, blood pressure regulation is essential for ensuring the tissues in the body receive the correct amount of blood for oxygen and nutrients while also eliminating waste products.

Cardiac muscle cells are different from smooth muscle and skeletal muscle in the sense that they originate from neural crest cells. Much of their physiology is driven by electrical current. The "pacemaker" of the heart is the sinoatrial node (SA node) which fires at regular intervals, causing the heart to beat (Figure 1 L). The atrioventricular node (AV node) relays this current between the upper and lower heart chambers, and the atrioventricular bundle continues to conduct the electrical impulses that regulate heartbeat (Figure 1 M). The bundle branches connect the atrioventricular bundle to the lower ventricle, while Purkinje fibers are embedded in the subendothelial tissue to conduct impulses through the heart (Figure 1 N-O). The interdependence of the chambers, valves, electrical circuits, and heart tissues renders it highly complex and vulnerable to disruptions and disorders. Therefore, more research is required to understand the mechanisms that drive a healthy heart and how to specifically diagnose and treat complex heart-related disorders.

Figure 1. Partial cross-section of the human heart to show selected anatomical structures. Figure created using

Complex Organ, Complex Disorders: The burden of heart disorders and current diagnostic tools.

Heart disorders are prevalent worldwide and pervade our healthcare systems, causing stress economically and emotionally to patients and others affected. For example, heart failure is a complex clinical syndrome characterized by the reduced ability of the heart to pump and/or fill with blood, affecting at least 26 million people worldwide. Alarmingly, this disorder is predicted to continue to increase in prevalence. Heart failure can occur due to underlying pathologies such as heart valve disorders, heart tissue disorders, and heartbeat disorders. Examples of these diseases are summarized in the schematic below:

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Figure 2. Complex heart disorders can be caused by valve malfunctions, tissue disorders, or heart beat irregularities. These underlying conditions can result in a myriad of cardiac pathologies.
Given the complexity of these disorders, advances in diagnostic tools are essential for the future of identification and early intervention. Currently, imaging techniques are the gold standard for diagnosing heart disorders. For example, an echocardiograph test is used to identify heart valve problems, a chest x-ray is used to identify abnormal heart tissue, and an electrocardiogram test is used to identify an irregular heartbeat. An additional test used to diagnose heart disorders is cardiac catheterization. A thin, flexible tube (called a catheter) is inserted into a blood vessel and travels to your heart to take images that reveal possible valve abnormalities.

Furthermore, a cardiac MRI can show if specific cardiac tissues are enlarged or atrophied to help diagnose a heart condition. To substantiate a diagnosis, blood-based biomarkers can indicate the presence of cardiac pathology. For example, elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations indicate high pressure inside the atria, providing evidence of a heart disorder. Similarly, genetic tests can reveal a predisposition or underlying reason for the presence of a heart condition such as cardiomyopathies. While image-based and molecular tests are used to identify cardiac disorders, it is imperative to continue investigating other possible biomarkers to diagnose and intervene sooner and improve patient outcomes.

Emerging Tools to Identify and Study Complex Disorders of the Heart.

Fortunately, we can study the heart and increase our understanding of these complex heart disorders to develop better diagnostic tools and treatments. Growing research supports evidence that blood-based cytokines and inflammatory markers correlate with heart pathologies. For example, c-reactive protein (CRP) plays an essential role in various pathological pathways such as myocardial infarction, pulmonary disorders, and atherosclerosis. It is possible that this can be further developed into a biomarker for the early detection of these pathologies. Moreover, Liaquat et al. (2014) has shown that increased CRP levels correlate with idiopathic dilated cardiomyopathy, a heart disorder characterized by an enlarged or weakened left ventricle.

Another promising blood-based marker that can indicate a cardiac disorder is brain natriuretic peptide (BNP). The heart's ventricles secrete BNP in response to excessive stretching of cardiomyocytes. The physiologic consequences of BNP secretion include a decrease in systemic vascular resistance and central venous pressure and an increase in natriuresis. As previously mentioned, BNP levels can indicate the severity of heart failure and inform treatment decisions to improve patient outcomes. Additionally, cytokines and inflammatory markers such as TNF-α, TGF-β, IL-1/-4/-6/-8/-18 are key players in the pathogenesis of inflammatory cardiac pathologies and can be monitored and measured via blood samples. For example, increased levels of the aforementioned markers are consistent with in ischemic heart disease. In fact, Buscemi et al. (2012) used Enzo's IL-6 (human) ELISA kit and TNF-α (human) ELISA kit to show that these two markers specifically were concurrent with increased risk for cardiovascular disease. Second messenger molecules can also be harnessed to understand the pathogenesis of heart conditions as well as evaluate the efficacy of current treatment methods. For example, cyclic-AMP (cAMP) intracellular concentrations play an important second messenger role in regulating cardiac muscle contraction. In fact, increased cAMP increases contractility, heart rate, and conduction velocity. Specifically, when there is excess cAMP, it is broken down by cAMP-dependent phosphodiesterase (PDE) in order to maintain the appropriate levels of cAMP for normal heart function, thus, this relationship is important for heart health. Patel et al. (2018) used Enzo's cAMP complete ELISA kit to reveal that Prostacyclin analogues can be successfully used to increase cAMP when deficient, and that the mechanism of the common hypertension drug, treprostinil, has two different mechanisms of action in healthy (cAMP-dependent) vs. diseased (non-cAMP-dependent) cells. These data provide insight into this relationship and how current drugs affect the physiology of the heart.

Developing assays to test for blood based markers such as CRP, BNP, cytokines, and interleukins is critical to advance our understanding of heart disorders and create mechanisms for early intervention to improve patient outcomes.

Enzo Can Help You Understand Complex Cardiac Disorders!

Enzo Life Sciences offers a comprehensive selection of products to enable the discovery of cardiac risk factors as well as analysis of the cellular response to novel therapeutics for cardiovascular medicine. For instance, the extensive repertoire of cytokine ELISAs have been cited in dozens of peer-reviewed publications, including cardiology research. Furthermore, they are offered to detect both human and mouse analytes, providing flexibility in your workflow




Adiponectin IL-2 IL-33 IL-1Β Lipocalin 2 (NGAL)
CD40 IL-6 Nampt IL-2 Nampt
CD40L IL-8 Osteoprotegerin IL-4 TGF-Β1
IFN-iγ IL-12p70 TNF-α Leptin

Figure 3. Enzo offers a variety of cytokine and interleukin ELISAs to detect both human and mouse analytes.

Enzo also offers many products to assess biomarkers for prevention, diagnosis, and monitoring of cardiac disorders such as the COX activity kit to assess inhibitors of inflammation without the use of radioactivity. Enzo's immunohistochemistry-validated antibodies such as the atrial natriuretic peptide monoclonal antibody will help you identify targets of cardiac distress with high signal and low background. For consistent and high quality results, partner with Enzo to further your cardiology research. Reach out to one of our application scientists today to get started!

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  1. The History of the Heart (
  2. How the Heart Works | NHLBI, NIH
  3. Heart Valve Disease | NHLBI, NIH
  4. G. Savarese et al. (2017) Global public health burden of heart failure. Card. Fail. Rev. 3, 7. Abstract.
  5. R. Dhingra, et al. (2016) Biomarkers in cardiovascular disease: Statistical assessment and section on key novel heart failure biomarkers. Trends Cardiovasc. Med. 27, 123. Abstract.
  6. A. Liaquat, et al. (2014) Polymorphisms of tumor necrosis factor-alpha and interleukin-6 gene and C-reactive protein profiles in patients with idiopathic dilated cardiomyopathy. Ann. Saudi Med. 34, 407. Abstract.
  7. M. Bartekova, et al. (2018) Role of cytokines and inflammation in heart function during health and disease. Heart Fail. Rev. 23, 733. Abstract.
  8. S. Buscemi, et al. (2012) Effects of red orange juice intake on endothelial function and inflammatory markers in adult subjects with increased cardiovascular risk. Am. J. Clin. Nutr. 95, 1089. Abstract.
  9. J.A. Patel, et al. (2018) Prostanoid EP₂ receptors are up-regulated in human pulmonary arterial hypertension: a key anti-proliferative target for treprostinil in smooth muscle cells. Int. J. Mol. Sci. 19, 2372. Abstract.

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