From Savannah to Science: What Giraffes Can Teach Us About Treating High Blood Pressure

Manas Mantri | SQ Online (2024-2025)

Saltman QuarterlyStudent
··9 min read

Introduction

In the animal kingdom, the giraffe stands tall as a marvel of evolutionary adaptation. With some reaching heights over 19 feet tall, giraffes reside as the tallest mammal in the world. While these gentle giants inspire awe with their towering height and serene demeanor, their anatomy may hold the secret to something even more captivating. Carrying hearts powerful enough to pump blood up their elongated necks and blood pressure levels that reach up to 280/180 mmHg, these creatures offer a fascinating glimpse into nature’s ingenuity. Presently, high blood pressure is one of the most common health issues that plagues this generation and is responsible for the onset of several heart-related ailments. Amazingly, giraffes are exempt from these complications, and recent scientific studies suggest that understanding how giraffes manage their exceptionally high blood pressure on a physiological level could hold the key to groundbreaking treatments for hypertension in humans. By delving into the biology of these majestic mammals, researchers are uncovering potential therapies that may one day help millions manage their blood pressure more effectively.

The Physiology of Hypertension

To comprehend the mechanisms that allow giraffes to be cardiovascular marvels, it is first important to understand the basics of hypertension as well as the general anatomy of the human cardiovascular system. The main components of the cardiovascular system include the heart, arteries, and veins. The heart, which consists of several chambers, is responsible for pumping out oxygen-rich blood to the rest of the body. Similarly, arteries are blood vessels that carry oxygen-rich blood away from the heart, while veins are responsible for bringing deoxygenated blood back to the heart. As the heart pumps blood to the rest of the body through the trail of arteries, the developed flow pushes force onto their walls. This phenomenon is known as blood pressure. Blood pressure is determined by both the systolic blood pressure value and the diastolic blood pressure value. Systolic blood pressure refers to the pressure in the arteries when the heart beats, while diastolic blood pressure refers to the pressure in the arteries between heartbeats, or when the heart is at rest. In a healthy human adult, blood pressure measures around 120/80 mmHg (systolic/diastolic). However, individuals with blood pressure values of 130/90 mmHg or above are considered hypertensive. Hypertension means that the force of blood pushing against the walls of the arteries is consistently too high, leading the heart to work harder to pump blood. This constant high pressure can damage the walls of the arteries, known as the tunica intima. Over time, continuous damage to artery walls can lead to a buildup of plaque. The increased calcification from plaque can raise the likelihood of blood clots and lead to an obstruction of blood flow to the heart, ultimately increasing the probability of a heart attack. Likewise, as blood pressure increases, the ventricles of the heart work harder to pump the same amount of blood to the body, causing the ventricle walls of the heart to thicken and become less flexible. The stiffened walls reduce the volume of the ventricle, causing less blood to be pumped out of the chamber, and even heart failure.

The Troubling Prevalence of Hypertension and Heart Disease

The primary reason why there is so much interest in unlocking the cardiovascular secrets of giraffes lies in the extreme prevalence of hypertension in today’s society. It is estimated that around half of the adult population in the United States suffers from hypertension, and a vast majority of those are not even aware that they are affected. Living in oblivion is particularly dangerous as hypertension remains the leading risk factor for heart disease, heart failure, and other cardiovascular-related issues. Currently, hypertension and heart disease combine to be the leading cause of death across a majority of racial and ethnic groups in the United States. In 2022, 702,880 people died of heart disease in the United States, amounting to one death every 33 seconds.

Current Treatment for Hypertension

Despite hypertension being so prevalent, the proportion of treated hypertensive patients remains very low worldwide, emphasizing the need for new and innovative treatment methods. Research shows that despite the large number of observational studies and controlled trials regarding hypertensive therapies in the past, recent years have been characterized by a lack of impactful research, concerning both novel and effective hypertension treatments. This can be attributed to the huge time lag that exists before a newly discovered drug is able to be marketed and distributed to the public, with the process sometimes taking a surplus of 10 years. Furthermore, according to FDA records, the cost of market authorization can pile up to over 2.5 billion dollars. However, an area of treatment that hasn’t been widely explored consists of developing clinical applications based on the myriad of genetic polymorphisms that are associated with hypertension. These polymorphisms refer to alterations in the DNA sequences of specific genes in the human body. Therefore, the key to modern hypertension treatments could lie within our genetic code, and a deep dive into giraffe DNA could point us in the right direction.

The Fascinating Cardiovascular System of Giraffes and Findings

From a scientific standpoint, almost every aspect of a giraffe’s anatomical structure suggests that these animals should struggle with hypertension. With necks that stretch over six feet long, their blood faces a significant upclimb from the heart to the brain, forcing their hearts to work extremely hard. Unsurprisingly, the average systolic blood pressure in giraffes measures around 250 mmHg, which is more than double the normal value measured in humans. Therefore, when measured with human standards, giraffes are evident victims of hypertension. However, giraffes are completely free of any hypertension-related problems. These mammals have evolved to protect their heart against the pathological changes associated with hypertension, and further research into these mechanisms can potentially spark innovative research related to human hypertension.

As mentioned earlier regarding hypertension, when the heart works harder to pump an adequate amount of blood to the body, the walls of the left ventricle thicken and are filled with less blood than before. This reduces the heart’s ejection fraction, which refers to the amount of blood the heart pumps per beat. The stiffening and scarring of the left ventricle is known as fibrosis. Similarly, as giraffe necks grow longer, their left ventricle thickens to account for an increase in afterload, which refers to the amount of pressure needed to eject blood from the left ventricle and into the rest of the body. However, an examination of giraffe hearts reveals that although their left ventricles condense, they do so without any signs of fibrosis. The ratio between left ventricular thickness and volume present in a giraffe heart would lead to an insufficient flow of blood if present in humans. Thus, this adaptation possessed by giraffes is a point of interest. Specific genetic exploration into this mechanism discloses that giraffes contain mutations in five different fibrosis-related genes. Explicitly, the lack of fibrosis that is associated with giraffe hearts can be linked to differences in the amino acid sequence of the angiotensin-converting enzyme (ACE) protein as well as mutations in the fibroblast growth factor receptor gene, FGFRL1. In humans, the angiotensin-converting enzyme is responsible for the conversion of angiotensin I to angiotensin II, playing an important role in elevating blood pressure when necessary. The FGFR gene regulates several important biological processes such as cell proliferation: The process by which cells grow and divide. When compared with other mammals, the FGFRL1 protein sequence in giraffe genes appeared highly different and contained seven amino acid substitutions in areas that are crucial for FGF binding.

Therefore, in an attempt to test whether the genetic mutations possessed by giraffes directly impacted heart function and blood pressure, scientists at the Northwestern Polytechnical University in China conducted research using mice models. To examine the in-vivo effects of the genetic substitutions, the relevant mutations were introduced to viable and fertile mice. Hypothesizing that the giraffe’s cardiovascular adaptations would only be relevant in a hypertensive setting, high blood pressure was induced in both wild-type and mutated mice using angiotensin II. To edit the seven specific amino acid substitutions present in the collected giraffe DNA, CRISPR technology was utilized on mice’s DNA. As expected, after 28 days of angiotensin II infusion, the wild-type mice exhibited hypertensive blood pressure levels, while the mutated mice showed average blood pressure readings. These results were deemed promising as the mutated mice exhibited both improved heart function and significantly less fibrosis than wild-type mice in both cardiac and renal tissues. The improved heart function was indicated by increased left ventricular ejection fraction, concluding that the mice were pumping a sufficient amount of blood to the rest of the body. These findings open the door to several potential hypertensive and cardiovascular therapies as the process of gene editing is quickly gaining traction. With animal trials involving rats showing such promise, it’s only a matter of time before trials can potentially progress to human subjects. Yet, further investigation into this mechanism is necessary to understand its full scope and possible impact on humans.

Overall, the promise that resides within the giraffe’s cardiovascular system remains undoubted. Research from the same study discovered that giraffes also contain variations in several metabolic pathways relevant to their high blood pressure adaptations. One of these adaptations lies in the platelet activation pathway, which is potentially responsible for freeing giraffes from the effects of hypertension-induced blood clotting. Another adaptation was found in the adrenergic signaling pathway in cardiomyocytes, which contributes to cardiac contraction and the specific morphology of the giraffe heart. These findings, as well as the potential shown in the FGFRL1 gene, hold great promise and shed a positive light on the future of hypertension treatment for humans.

Works Cited