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Source https://www.fightaging.org/archives/2018/11/a-mechanism-by-which-hypertension-accelerates-atherosclerosis/

The raised blood pressure of old age is known as hypertension, and it is predominantly caused by dysfunction in blood vessel walls: cross-links, calcification, and loss of elastin cause reduced elasticity, while smooth muscle cells lose their capacity to act for a variety of other reasons. When blood vessels can no longer correctly react to circumstances by contracting and dilating to an appropriate degree, then the whole system of pressure control is thrown off, and higher blood pressure is the result.

Atherosclerosis, on the other hand, is the progressive formation of fatty plaques in blood vessel walls. This narrows and weakens blood vessels. Atherosclerosis interacts with hypertension in the obvious way: weakened blood vessels and fragile plaques are more likely to suffer catastrophic structural failure in a high pressure environment, leading to a fatal stroke or heart attack. Just considering this interaction, it is clear that hypertension raises the risk of death and shortens life expectancy. This isn’t the only interaction, however, just the most direct one. In addition, hypertension accelerates the growth of atherosclerotic plaques, and the reasons for this are not fully understood.

In the research materials noted here, the authors report on an association between a particular subset of cases of hypertension and the pace at which immune cells known as monocytes arrive at atherosclerotic plaques in order to try to clean them up. Once embedded into the blood vessel wall, monocytes transform into macrophages. Plaques grow because these macrophages become overwhelmed by oxidized lipids, fail in their task of rescue, and die. Worse, many become inflammatory, senescent foam cells that linger to secrete signals that call in more of their peers. The bulk of a plaque is cell debris, and atherosclerosis is really a form of runaway garbage catastrophe. Once things get to the tipping point, the end is inevitable. In some cases, hypertension moves that tipping point in an undesirable direction by causing the production of more monocytes.

Neural driven blood pressure accelerates atherosclerotic cardiovascular disease through over production of monocytes

Atherosclerotic cardiovascular disease is a build-up of cholesterol plaque in the walls of arteries, causing obstruction of blood flow. Scientists have found that high blood pressure caused by specific signalling from the brain promotes heart disease by altering stem cells within the bone marrow. The results demonstrate how an overactive sympathetic nervous system that causes elevated blood pressure can instruct bone marrow stem cells to produce more white blood cells that clog up blood vessels.

“We now know that changes in the immune system contribute significantly to heart disease. We aimed to determine how the sympathetic nervous system through the brain directly promotes atherosclerosis in the setting of hypertension. We have discovered that this form of high blood pressure, often associated with stress, causes changes within the bone marrow leading to increased white blood cells circulating though our vessels. This is significant as the general view of hypertension is that it is mainly a disease of the blood vessels, which means other heart damaging events are missed.” The team is now exploring the specific molecules involved, which may shed light as to why some current therapies are ineffective.

Chronic sympathetic driven hypertension promotes atherosclerosis by enhancing hematopoiesis

Hypertension is a major, independent risk factor for atherosclerotic cardiovascular disease. However, this pathology can arise through multiple pathways, which could influence vascular disease through distinct mechanisms. An overactive sympathetic nervous system is a dominant pathway that can precipitate in elevated blood pressure. We aimed to determine how the sympathetic nervous system directly promotes atherosclerosis in the setting of hypertension. We used a mouse model of sympathetic nervous system-driven hypertension on the atherosclerotic-prone apolipoprotein E deficient background. When mice were placed on a western type diet for 16 weeks we showed the evolution of unstable atherosclerotic lesions. Fortuitously, the changes in lesion composition were independent of endothelial dysfunction, allowing for the discovery of alternative mechanisms.

With the use of flow cytometry and bone marrow imaging, we found that sympathetic activation caused deterioration of the hematopoietic stem and progenitor cell niche in the bone marrow, promoting the liberation of these cells into the circulation and extramedullary hematopoiesis in the spleen. Specifically, sympathetic activation reduced the abundance of key hematopoietic stem and progenitor cell niche cells, sinusoidal endothelial cells, and osteoblasts. Additionally, sympathetic bone marrow activity prompted neutrophils to secrete proteases to cleave the hematopoietic stem and progenitor cell surface receptor CXCR4. All these effects could be reversed using the β-blocker propranolol during the feeding period. These findings suggest that elevated blood pressure driven by the sympathetic nervous system can influence mechanisms that modulate the hematopoietic system to promote atherosclerosis and contribute to cardiovascular events.

Source https://www.niashanks.com/fitness-goals-for-women/

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“Screw fat loss,” she declared, “I’m going to get strong.”

Those words poured from a client’s lips almost six years ago, and she hasn’t turned back since. She isn’t the only one choosing fitness goals that don’t have a damn thing to do with fat loss, and reaping the myriad rewards a new path provides.

According to most magazines, commercials, products, and articles targeting women, it’s easy to assume losing fat, fixing flaws, and looking better are the only reasons a woman can have to eat well and move her body.

If a woman eats a healthy meal, it’s because she’s “watching her weight.” If she’s on a cardio machine or even squatting and deadlifting heavy weights, it’s because she’s trying to “tone up” and fix her flawed features.

Many of my clients, and women in general, have a history of constantly striving for fat loss — for years that’s all they focus on. Burning fat and shrinking down is the sole reason they go on a diet or exercise or even strength train. They diet- and program-hop searching for the “holy grail” fat loss program that will finally help them shed their stubborn fat stores and deliver happiness.

I’ve done it all too, and thankfully I’ve discovered numerous other (better) health and fitness goals women can have instead of losing fat and fixing flaws:

To feel good in their body.

To increase their stamina and energy levels.

To increase their physical strength.

To increase their physical strength even more.

To learn new skills.

To move pain free and alleviate old aches and pains.

To improve their quality of life.

To build muscle. (Yes, women can actually want to build muscle.)

To increase bone mineral density to ward off osteopenia and osteoporosis.

To challenge themselves physically as a means to increase mental fortitude.

To maintain independence with age.

To regain independence after an injury or surgery.

To increase balance, stability, and coordination.

To relieve stress.

To complement their performance in other activities like running, tennis, dance, lumberjack competitions, or whatever the hell else they want to do better.

To do something they enjoy.

To shatter self-imposed limitations.

To improve sleep quality.

To train for an event they’d never do otherwise, like run a 5K race, compete in a powerlifting meet, or participate in a group Spartan Race.

To be able to declare, “I did that. What else can I do?”

To contribute to self-care.

To be more instead of feeling obligated to chase all things “less.”

To do something, simply for the hell of it, because they can.

To invest in their immediate and long-term health.

To reveal to themselves how strong they truly are.

To achieve awesome goals like busting out their first unassisted chin-up, deadlifting twice their bodyweight, running a 10K, or anything else they deem important.

To lead as an example for their children, and family and friends.

To maintain their sanity. (I refer to my strength training sessions as “barbell therapy” for a reason.)

To do something because it’s important to them and makes them happy, and what anyone else thinks is irrelevant.

To discover their unique strengths and abilities, and to magnify them.

To make health and fitness something they get to do instead of something they have to do.

To take a natural “good” ability, and become great at it.

To build a body that serves them, and allows them to do the things that bring them joy, happiness, and a fulfilling life.

To lift weights, or move their body in other ways, because each workout is its own reward.

If you’re burned out and exhausted from constantly chasing fat loss or focusing on aesthetics and using the scale as the sole indicator of your success, tackle some of the goals shared above. Harness the power that gets unleashed when you say, “Screw fat loss, I’m going to get strong.” You’ll be amazed, as so many have been, at what happens to your mind, and body, when you change your approach to nutrition, health, and fitness.

Like what you read? Never miss a thing — join the free newsletter below. You’ll receive the Beautiful Badass Mini Course as a welcome gift.

The post Fitness Goals for Women (That Don’t Have a Damn Thing to do With Fat Loss) appeared first on Nia Shanks.

Source https://www.fightaging.org/archives/2018/11/a-distinct-population-of-smooth-muscle-cells-is-associated-with-vascular-disease/

Researchers have identified a marker for a small population of smooth muscle cells in blood vessel walls that show up in larger numbers in cases of vascular disease, such as atherosclerosis. These cells may be dysfunctional in the sense that they (a) appear to be involved in inflammatory signaling and (b) lose the normal behavior of smooth muscle tissue. My first thought on reading the abstract of the paper was that this may be a senescent population, as inflammation and disruption of tissue function are quite characteristic of the bad behavior of senescent cells. On closer reading that sounds less likely, however. These may well be cells that are engaged in repair and regrowth activities, which also tend to involve at least short term inflammation alongside significant changes in cell activities.

Are these cells harmful, or are they responding in a beneficial way? That may depend on context; it might be the case that they are initially beneficial, but in the later stages of disease progression they become a problem, and contribute to the disease state. The discovery of a marker allows technologies such as the Oisin Biotechnologies suicide gene therapy platform to target these cells for destruction. Evaluating the outcome in mice is the fastest way to determine whether or not the cells are harmful, and whether or not this varies with disease progression. This is the case for the removal of a broad range of other potentially harmful cell populations found in older individuals. Most of these projects are easy to describe, and all of the necessary preliminary work of identifying the cells has been accomplished, but still no-one is even thinking about undertaking the work. The challenge here is that there is too little philanthropy, too few entrepreneurs, and too little venture funding to carry out anywhere as much as many projects as should be underway right now.

Observation of blood vessel cells changing function could lead to early detection of blocked arteries

The muscle cells that line the blood vessels have long been known to multi-task. While their main function is pumping blood through the body, they are also involved in patching up injuries in the blood vessels. Overzealous switching of these cells from the pumping to the repair mode can lead to atherosclerosis, resulting in the formation of plaques in the blood vessels that block the blood flow. Using state-of-the art genomics technologies, an interdisciplinary team of researchers has caught a tiny number of vascular muscle cells in mouse blood vessels in the act of switching and described their molecular properties. The researchers used an innovative methodology known as single-cell RNA-sequencing, which allows them to track the activity of most genes in the genome in hundreds of individual vascular muscle cells.

“We knew that although these cells in healthy tissues look similar to each other, they are actually quite a mixed bag at the molecular level. However, when we got the results, a very small number of cells in the vessel really stood out. These cells lost the activity of typical muscle cell genes to various degrees, and instead expressed a gene called <a href="https://en.wikipedia.org/wiki/Sca-1"Sca1 that is best known to mark stem cells, the body’s master cells.” Knowing the molecular profile of these unusual cells has made it possible to study their behaviour in disease. Researchers have confirmed that these cells become much more numerous in damaged blood vessels and in atherosclerotic plaques, as would be expected from switching cells. “Theoretically, seeing an increase in the numbers of switching cells in otherwise healthy vessels should raise an alarm. Likewise, knowing the molecular features of these cells may help selectively target them with specific drugs.”

Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels

Vascular smooth muscle cells (VSMCs) show pronounced heterogeneity across and within vascular beds, with direct implications for their function in injury response and atherosclerosis. Here we combine single-cell transcriptomics with lineage tracing to examine VSMC heterogeneity in healthy mouse vessels. The transcriptional profiles of single VSMCs consistently reflect their region-specific developmental history and show heterogeneous expression of vascular disease-associated genes involved in inflammation, adhesion, and migration.

We detect a rare population of VSMC-lineage cells that express the multipotent progenitor marker Sca1, progressively downregulate contractile VSMC genes and upregulate genes associated with VSMC response to inflammation and growth factors. We find that Sca1 upregulation is a hallmark of VSMCs undergoing phenotypic switching in vitro and in vivo, and reveal an equivalent population of Sca1-positive VSMC-lineage cells in atherosclerotic plaques. Together, our analyses identify disease-relevant transcriptional signatures in VSMC-lineage cells in healthy blood vessels, with implications for disease susceptibility, diagnosis, and prevention.