Heart Health in the Light of Evolution: What Can Chimps Teach Us About Cardiovascular Disease?

Wah! Chimps. Chimps have very limited coronary artery atherosclerosis. This is a type of heart disease, and this is really interesting because chimps, despite being our close relatives, have much higher LDL cholesterol levels than us, the so-called bad cholesterol, about 60% higher mean LDL cholesterol levels in chimps as compared to humans. And chimps can live quite a long time, especially in captivity, greater than 50 years in captivity. And they don't tend to develop coronary artery atherosclerosis. By contrast, humans can develop coronary artery atherosclerosis very early on, even in 20s and 30s. Even pre-industrial societies, you can find evidence of this, as in the ancient Egyptians. So why the distinction? Why are chimps resistant to coronary artery atherosclerosis even with very high LDL levels? I'm going to share with you some inflammatory gems that got me thinking from a brand new perspective paper that I thought was really cool. Welcome to my channel. Stay curious. The paper in question is entitled "Atherosclerosis as a Demically Sword of Human Evolution: Insights from Nonhuman Ape-like Primates, Ancient Human Remains, and Isolated Modern Human Populations" by Kumar et al. The thesis of this paper, the 50,000-foot view, is that atherosclerosis is driven by inflammation. They talk a lot about the inflammatory model of atherosclerosis. And what distinguishes humans, us, Homo sapiens, from chimps and other non-human primates in terms of our predilection, our predisposition to coronary artery atherosclerosis, is that our immune systems are adapted to be much more inflammatory. And that during evolution, this was beneficial to our reproductive fitness, but now it's it's coming at the cost of really high rates of coronary artery atherosclerosis, despite having lower LDL levels than chimps and other non-human primates. So, they talk a lot about pathogen-driven selection, um, an ancient molecular arms race, they call it, whereby as we descended from the trees, started walking around on land, and got exposed to more and more pathogens, bugs, parasites, bacteria, viruses, it made sense for our immune system to rev up and be more on edge so that when we were exposed to a pathogen, the immune system would attack it, sometimes rather nonspecifically. But that could be a benefit, especially to reproductive benefit early on in life. The cost is that if you have a more pro-inflammatory immune system, it can also wreak havoc on the body itself. And they give a lot of examples from our genome to say, look, these are the little things that distinguish us from chimps, and they really cause our immune system to be more pro-inflammatory So one example of a whole class of biomolecules they give are the Siglecs, a group of immunoregulatory molecules that alter immune cell reactivity and make humans susceptible to systemic, whole-body inflammation. In humans, say, versus chimps, our inhibitory Siglecs, those Siglecs that dampen down the immune system, in humans they're lost. You can see that here in green. Versus the activating Siglecs, the ones in red, that make our immune system much more revved up. They're activated in humans as compared to chimps. So you see that there's this massive shift in balance in the Siglecs to drive humans towards inflammation, and as opposed to being in chimps, more anti-inflammatory. Another example they give in the paper is that of caspase 12. Caspase 12 is an inhibitor of the inflammasome response, which, as the name suggests, is pro-inflammatory. So most humans have lost caspase 12, and this is evolution effectively breaking the brake on our inflammasome, leading us to be more chronically inflamed as compared to our ancestors. Now, loss of caspase 12 could make us more resilient to certain pathogenic infections, but also primes us to be more chronically inflamed. This is the same as with the Siglecs, so you're seeing a pattern in our genome as compared to our non-primate ancestors. As we evolved, this could have been a beneficial trade-off, favoring survival in the early years at the cost of fitness maybe later in life. But in the modern era, the weight of the pros and the cons have changed as fewer people are dying of bacterial infections and more and more we're inundated with chronic inflammatory disease that have become the major burden on our population. They also bring in the element of neurobiological stress in humans, which I thought was really interesting, and there was a section from the paper I really liked, so I'm just gonna read it to you. Humans, inhumans, Increased cognitive abilities and complicated social relationships have come at the expense of greater susceptibility to complex forms of psychological stress. For instance, increased amygdala activity— the amygdala being a part of the brain involved in the fight-or-flight fear response, anxiety, those kind of emotions— increased amygdala activity associated with stress is strongly associated with arterial inflammation and consequent cardiovascular disease. For instance, post-traumatic stress disorder has been shown to promote cardiovascular disease through proposed mechanisms including enhanced oxidative stress, mitochondrial dysfunction, etc., etc. Basically, they're drawing a connection between our highly evolved brains and the burdens that comes with, including anxiety, stress, stress response, and arterial inflammation in cardiovascular disease—coronary artery atherosclerosis. I thought this was really interesting, definitely food for thought. So let's take a step back and think about what is the relevance? What is the relevance to you and me as humans? Because we're not changing our genes anytime soon, and we certainly don't want to revert to being chimps. We are where we are in terms of evolution. Well, here are my thoughts. Despite innovations in pharmacotherapy, medications targeting LDL and ApoB, there is a persistently high mortality burden associated with coronary artery atherosclerosis. That's not controversial. That's a fact. And this is likely due to high rates of residual risk factors not well addressed by medications. Things like metabolic syndrome, conditions associated with insulin resistance, and chronic systemic inflammation. All these things tend to go hand in hand. And in my opinion, this really highlights the importance of metabolic lifestyle interventions to quell inflammation, as organisms—humans, organisms—genetically primed to be susceptible to inflammation, a case they really make well in this article. And living in a world that is booby-trapped with chronic inflammation booby traps. It's pretty ridiculous when you go around our food environment and our, you know, just modern environment, how everything seems to promote chronic inflammation, high rates of stress, terrible food environment, etc., etc. So, you know, this I think places emphasis on the importance of doing things like reducing packaged processed food intake, reducing sugar intake, getting enough sleep, stress reduction, exercise routines, all these things that You know, it's not revolutionary to say they're important, but they take on new meaning when seen in the light of evolution. I hope you agree with me, and thanks for bearing with me as I monkeyed around. Pardon the pun. Have a good day.