A Matter of Heart

With a nod to Cupid, February has been dubbed “Heart Month” by the American Heart Association to raise awareness about heart health and cardiovascular disease. According to the Centers for Disease Control and Prevention, heart disease has been the leading cause of death in humans in the United States since 1951. Coronary artery disease (CAD), caused by plaque buildup in the walls of the coronary arteries that supply blood to the heart, is the most common form of heart disease. As far as our pets go, however, cardiovascular disease is uncommon, and CAD is almost unheard of. In contrast to humans, cancer is cited as the leading cause of death in dogs and cats. The difference in the prevalence of CAD between dogs and humans is particularly striking when one considers that the dog has been proposed to be a model for human aging and mortality.

Although the pathophysiology of CAD is complex and not entirely elucidated, certain factors, including high blood pressure, high low-density lipoprotein (LDL) cholesterol plasma concentrations, smoking and second-hand smoke exposure, obesity, and physical inactivity, have been shown to contribute to an increased risk of its development in humans. Given that many of our canine companions share some of these risk factors, such as obesity and lack of physical activity, it is interesting to ask why CAD is so rare in this species?

The answer could be as simple as the fact that dogs don’t live as long as humans. Atherosclerotic lesions can be detected in humans as early as their teenage years, but the clinical ramifications of the disease typically don’t occur until many years later. So perhaps, if our sedentary, overweight dogs lived long enough, they might develop CAD. However, it is more likely that evolution has gifted the dog with a physiology that is protective against atherosclerosis. For example, dogs, as well as mice, rats, and pigs, have no or very low plasma concentrations of cholesteryl ester transport protein (CETP). CETP plays an important role in the transfer of cholesterol from high-density lipoproteins (HDL), often referred to as the “good” form of cholesterol, to apo B-containing lipoproteins, such as LDL and very low-density lipoproteins (VLDL), commonly called “bad” cholesterols. The result is that dogs generally have a plasma lipoprotein distribution that is high in HDL and low in LDL and VLDL; a pattern that is associated with a lower risk of CAD in man.

If the lipid profile of the dog is changed experimentally, however, it will develop atherosclerotic lesions and CAD. For example, dogs fed diets very high in saturated fat and cholesterol will develop atherosclerotic plaques, but only if the functioning of their thyroid gland is also impaired. Genetic manipulations of certain genes can also result in the development of CAD. For example, another lipoprotein, Apolipoprotein E (ApoE) plays a critical role in cholesterol metabolism. When the CRISPR/CRISPR-9 gene editing platform was used to produce a non-functional ApoE protein in dogs, clearance of LDL and VLDL was delayed, leading to hyperlipidemia and the development of severe atherosclerotic disease. So, with dietary and endocrine manipulation or genetic alterations we can make the dog more like man. The question is, how do we use this information to make man’s cardiovascular system more like a dog’s?

In addition to a naturally protective plasma lipid profile, it also appears that the dog has evolved a resilient pancreas which may also contribute to the low prevalence of CAD. In humans, there is a strong link between Type 2 Diabetes Mellitus (T2DM) and the development of CAD. T2DM is caused by impaired production and secretion of insulin by pancreatic beta-cells combined with insulin resistance in peripheral tissues. In humans, the pathophysiology of T2DM is strongly linked to an excess of calories consumed versus calories expended, leading to weight gain and obesity. While obese dogs do develop insulin resistance, their pancreas compensates by increasing insulin secretion. Therefore, unlike humans, overweight dogs are not at risk of developing T2DM.

Dogs do develop Diabetes Mellitus (DM) but traditionally it has been thought of as insulin-dependent or Type 1 (T1DM), characterized by persistently low plasma insulin concentrations and an absolute requirement for exogenous insulin administration. In humans, T1DM is most often associated with immune-mediated destruction of the pancreatic insulin secreting beta cells leading to the inability to produce insulin. There is little evidence, however, that autoimmunity is a significant component of DM in dogs. Rather, it has recently been proposed that comorbidities, such as pancreatitis or endocrinopathies, may play an important role in the onset of DM in the dog. Furthermore, if these conditions are addressed earlier in the disease process, the insulin-producing beta cells may be able to recover and normal glucose metabolism restored.

The question remains: given the major physiological differences between man and dogs, why are they still considered an appropriate model for study? For one, dogs are close companions for many of us, sharing our homes and lives. Therefore, they also share risk factors that may contribute to diseases that we have in common. Understanding the differences and similarities between dogs and man, particularly what physiological peculiarities protect them from our most frequent afflictions, can lead to new therapeutic strategies and better drug development. As we continue to try to unravel the underlying causes of many of these conditions, we must keep in mind that as much as we can learn from dogs and other species we use as animal models, we owe them a debt to use that knowledge to benefit them, as well as ourselves.


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First Five
First Five is our curated list of articles, studies, and publications.
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1/ Sleepy short nosed dogs
A recent study by Hungarian researchers demonstrated that brachycephalic breeds, which are dogs with very short noses, including the most popular breed in the United States, the French Bulldog, suffer from sleep apnea. It appears that flat-faced dogs sleep more during the day because their breed-specific sleep apnea interferes with sleep quality. These effects on sleep are not simply because their facial structure makes it difficult for them to breathe. Brachycephalic dogs have changes in their brain structure and function. For example, their REM sleep phase is longer than non-REM sleep, and their sleep EEG patterns show signs of white matter loss. Whether selective breeding to lengthen their nose could correct these issues while maintaining their cuteness factor remains to be determined.

2/ And speaking of sleep
An international team of researchers from France, South Korea, and Germany investigated electroencephalographically-defined sleep in wild chinstrap penguins at sea and while nesting in Antarctica. These birds, which are constantly exposed to egg predators and aggression from other penguins, have a unique sleep strategy. The penguins nod off >10,000 times per day, engaging in very brief bouts of slow-wave sleep lasting on average of only 4 seconds, sometimes only involving one side of the brain, but resulting in the accumulation of >11 hours of sleep for each hemisphere. This observation suggests that the benefits of sleep can accrue incrementally, at least in this species.

3/ How long do dogs live?
A recent study out of the UK using data collected from vets, pet insurance companies and animal welfare charities examined information about 584,734 dogs belonging to 155 breeds, of which 284,734 were deceased. The average lifespan was 12.5 years, with female dogs living slightly longer than males. The study also found that small, long-nosed dogs of both sexes had the highest life expectancy, surviving 13.3 years on average. With an expected lifespan of just 9.1 and 9.6 years old, male and female medium-sized, flat-faced dogs had the worst outcomes, respectively. Somewhat surprisingly, purebred dogs lived slightly longer than mixed breeds.

4/ The beautiful but endangered snow leopard
In the first study of its kind, India undertook a massive effort to estimate its Snow Leopard population. Setting up over 2,000 camera traps covering 120,000 square kilometers, the population was determined to be approximately 718 cats. That makes up about 10 to 15 per cent of the global population, which conservationists believe is between 3,000 and 5,400. It is hoped that this will be become a regular assessment that will identify challenges and threats to the species and aid the formulation of effective conservation strategies.

5/ And although no one was speaking of chickens
The ability of one species to interpret information contained within the vocalizations of other species can be an adaptive advantage. Most of us can recognize whether our dogs are barking from excitement (i.e., chasing a squirrel) or concern (i.e., there is a stranger in the yard). In a UK study, the ability of humans to detect the difference between chicken vocalizations was studied. One hundred and ninety-four participants listened to eight calls when chickens were anticipating a reward, and eight calls in non-rewarded contexts, and were asked to determine whether the chickens were experiencing pleasure/displeasure, and high/low excitement. Sixty-nine percent of participants correctly assigned reward and non-reward calls to their respective categories. Poultry farmers may not find these results at all surprising, and likely would report that they know the sound of a happy versus stressed flock, but the study does provide evidence that this is an inherent trait in humans, and not strictly learned from experience.

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