Giraffes Thrive Despite High Blood Pressure

Biological Strategy

Giraffe

Sam Stier

Image: Damian Patkowski / Unsplash / Public Domain - No restrictions

Prevent Fatigue

When materials that comprise living systems are subjected to repeated loads, they can weaken over time. This is called fatigue and it can lead to cracks and eventually failure. However, fatigue doesn’t occur just anywhere on a material; the cracks usually start in areas subjected to elevated local stresses. Therefore, living systems often employ shapes, materials, and/or smooth transitions to decrease the potential for fatigue. An example of using shape is found in brown algae, an intertidal seaweed. Rather than being bent by the constant flow forces of waves and currents, its shape causes it to be pulled. This reduces stress by roughly 800 times compared to another species that bends with the flow, ultimately reducing structural fatigue.

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Mammals

Class Mammalia (“breast”): Bats, cats, whales, horses, humans

Mammals make up less than 1% of all animals on earth, but they include some of the most well-known species. We know first-hand some of the characteristics that make mammals unique, like having hair, being able to sweat, and producing milk through mammary glands. Another critical shared feature is a set of highly-specialized teeth. Unlike sharks or alligators, for example, whose teeth are generally all the same size and shape, mammals have differently shaped teeth in different areas of the jaws to target specific foods or foraging strategies.

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Genes of giraffes maintain cardiac health despite high blood pressure by keeping thickened heart muscles supple.

Part of a series focused on the work of the Natterson-Horowitz Lab.

Introduction

An orange, globular sun resting on the horizon of the acacia-dotted savannah of Kruger National Park in South Africa reveals an iconic silhouette: an herbivore with such a long neck, it could peer through the upper windows of a two-story home. The need for giraffes to supply blood to their brains through their far-reaching necks results in systolic (i.e., arterial) blood pressures more than double that of humans, even accounting for body size differences. To handle blood pressures as high as 300 mmHg (millimeters of mercury), the left ventricle of a giraffe heart thickens over its lifespan. In humans, thickening of the left ventricle of the heart from hypertension can be lethal, but in giraffes, apparently not at all.

The Strategy

The ability of giraffe hearts to maintain their health and functionality despite the thickening of the left ventricle appears related to the relative lack of restrictive connective tissue (fibrosis) in the thickened heart wall. How does the thickened giraffe heart remain pliable? The lack of debilitating cardiac fibrosis appears related to mammalian genes that are highly-mutated in giraffes, such as FGFRL1 (Fibroblast Growth Factor Receptor Like 1).

When spliced into the genomes of mice using CRISPR-CAS9 gene editing techniques, this uniquely giraffe version of the FGFRL1 gene resulted in significantly less fibrosis in mice cardiac tissue, despite induced hypertension. Several other cardiac fibrosis-related genes in giraffe genomes show similarly high degrees of difference from comparable genes in other mammals.

The Potential

Diastolic heart failure (i.e., from thickened left ventricles) is a physically debilitating condition and one of the leading causes of death in people, especially women. A more precise understanding of the underlying mechanisms of the giraffe heart’s ability to maintain function, despite cardiac thickening, may yield pathways to therapeutic innovations vital to improving outcomes for people suffering all-too-common deadly heart conditions.

Last Updated February 9, 2023

References

“Across the tree of life, female animals share biological characteristics that place them at risk for similar diseases and disorders. Greater awareness of these shared vulnerabilities can accelerate insight and innovation in women’s health. We present a broadly comparative approach to female health that can inform issues ranging from mammary, ovarian, and endometrial cancer to preeclampsia, osteoporosis, and infertility. Our focus on female health highlights the interdependence of human, animal, and environmental health.” (Natterson-Horowitz et al.)

Journal article

Female Health Across the Tree of Life: Insights at the Intersection of Women's Health, One Health and Planetary Health

PNAS Nexus | May 2022 | Natterson-Horowitz B., Boddy A.M., and Zimmerman D

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Reference

“The giraffe heart, for example,appears resistant to pathology related to heart failure with preserved ejection fraction (HFpEF)—aleading form of hypertension-associated cardiovascular disease in humans. Here, we postulate thatthe physiological pressure-induced left ventricular thickening in giraffes does not result in the pathological cardiovascular changes observed in humans with hypertension. The mechanisms underlyingthis cardiovascular adaptation to high blood pressure in the giraffe may be a bioinspired roadmap forpreventive and therapeutic strategies for human HFpEF.” (Natterson-Horowitz et al.: 248)

Journal article

Did giraffe cardiovascular evolution solve the problem of heart failure with preserved ejection fraction?

Evolution, Medicine, and Public Health | 2021 | Natterson-Horowitz B, Baccouche BM, Head JM, Shivkumar T, Bertelsen MF, Aalkjær C, Smerup MH, Ajijola OA, Hadaya J, Wang T.

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Reference

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