Endothelium, Heal Thyself (Self-Mending Vessels)

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The endothelium, the cellular layer lining the body’s blood vessels, is extremely resilient.

Measuring just a few hundred nanometers in thickness, this super-tenuous structure routinely withstands blood flow, hydrostatic pressure, stretch and tissue compression to create a unique and highly dynamic barrier that maintains the organization necessary to partition tissues from the body’s circulatory system.

It’s also extremely adaptable. In instances when the barrier must be physically breached to enable immune cells to reach various regions of the body to fight infection, the endothelium cooperates with leukocytes to create openings to provide the infection-fighting cells ready access to their targets. By and large, these ensuing “micro-wounds” are short-lived; as soon as the cells have crossed the endothelium, these pores and gaps quickly heal, restoring the system’s efficient barrier function. In cases when these gaps fail to close — and leakage occurs — the results can be devastating, leading to dramatic pathologies including sepsis and acute lung injury.

The mechanism underlying this highly intuitive capability has not been well understood. Now a research team led by Christopher V. Carman, PhD, of the Center for Vascular Biology Research at Beth Israel Deaconess Medical Center (BIDMC), using a combination of advanced fluorescence imaging and electron microscopy to monitor intracellular signaling dynamics, has amassed real-time information that shows that biomechanical signals are what sets this healing process in motion. Described in The Journal of Cell Biology, the new findings suggest that rather than structural robustness per se, the barrier function of the endothelium relies on an enormous self-restorative capacity.

“When people talk about biomechanics, they’re saying that cells are able to sense and respond to changes in force,” says Carman, who is also an Assistant Professor of Medicine at Harvard Medical School. “In other words, it’s not only hormones and chemical signals that influence cell behaviors. Cells can actually sense physical cues and thereby modulate their function.” Specifically, the new findings demonstrate that the endothelium senses an acute loss of preexisting isometric tension, and that downstream of this biomechanical signal, the ensuing recovery response generates reactive oxygen species (ROS), which are responsible for coordinating the micro-wound closure process.

Carman’s previous work explored precisely how leukocytes generate vascular micro-wounds in the first place, uncovering a novel endothelial piercing activity — “invasive podosomes” — that are generated by the leukocytes. In this new paper, he hypothesized an equally active role for the endothelium in closing the pores and gaps made by the leukocytes.

To test this hypothesis, his laboratory set up experimental models that mimicked acute, intense inflammation. Using dynamic time-lapse and high-resolution confocal microscopy, the investigators could see the process by which leukocytes were breaching the endothelial cell. In the course of a 10-minute span, they observed that a single endothelial cell tolerated the passage of at least seven leukocytes directly through its body, and that within this brief period, the gaps closed, leaving no sign of the pores.

“The cell’s restorative capacity was just so striking,” says Carman. “But these early investigations were still inadequate to tell us how the breaches were being closed. We had to dig down to the sub-cellular level to understand the underlying activities and the molecular signaling mechanisms that were orchestrating these activities.”

Subsequent experiments, led by co-first author Roberta Martinelli, PhD, revealed that in response to micrometer-scale disruptions caused by the transmigrating leukocytes, the endothelial cells were generating unique ventral lamellipodia structures, which were then migrating to the sites of the micro-wounds to close them up. “The ventral lamellipodia were responding to the sensation of an acute loss of preexisting isometric tension,” explains Martinelli, a senior scientist in the Carman laboratory, who compares the cell to a circus tent tethered in place by strategically placed ropes and stakes.

“If you cut one of the ropes holding up the tent, two things will happen,” she adds. “First the part of the tent that was under tension will undergo a recoil which will lead to a relaxation, leaving one part of the tent untethered and flapping in the breeze. At the same time, the remaining sets of ropes and stakes will have to bear the extra load. In the case of the endothelial cells, this translates to a force loading event.”

Existing studies have focused almost exclusively on force loading (physical pulling or tugging on cells) as response triggers. But by using new devices, the team was able to push, prod, stretch and unstretch cells in very specific ways.

Vascular endothelial cell healing a transcellular wound.

“Our experiments told us that endothelial micro-wounding is actually a tension-loss signal [i.e. force unloading] and that this signal cued the recovery response,” adds Carman.

This response, he adds, is fundamentally dependent on proteins (i.e. NADPH oxidases) that can generate reactive oxygen species (ROS), specifically hydrogen peroxide.

ROS are widely implicated in causing cellular, tissue and organ damage when present at excessive levels in the body. But, these findings show that low levels of these molecules — when produced in discrete locations within the cell — are highly protective.

“It’s tempting to speculate that excess ROS causes vascular breakdown by short-circuiting the recuperative response process and creating ‘white noise’ that dis-coordinates and disrupts micro-wound healing,” adds Carman. “It appears that we’ve got an essential homeostatic self-repair mechanism that is completely dependent on the generation of intracellular ROS, which is opposite to our typical thinking about ROS in cardiovascular health and disease.”

Adds William Aird, MD, PhD, Director of BIDMC’s Center for Vascular Biology Research, “These findings suggest a new way of thinking about how to deal with pathologic breakdown of the endothelial barrier. We know that a ‘leaky endothelium’ is a central part of the pathogenesis of a number of serious diseases, including sepsis, acute lung injury, and ischemic cardiovascular diseases, as well as chronic inflammatory conditions such as diabetes and arthritis. In addition to the presence of excessive barrier insults, it now appears that leakage can result when the endothelium loses its self-restorative capacity and its dynamic reserve to heal micro-wounds.”

Credit: Christopher Carman

Dr. Ryan’s Disease Fighting Purple Drink

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Purple Smoothies


This powerful purple smoothie created by Dr. Jeanette Ryan packs a lot of punch because it is made from whole fruits which exposes more of the plant nutrients to your digestive track for easy absorption.

The Purple Smoothie is built upon the “Green Base” which you can find the recipe for here.

Pour 10 ounces of the green base back into the VitaMix. Add 1 cup of frozen organic fruit like Trader Joe’s Wild Boreal Blueberries or Cascadian Farms Organic Blueberries (available at Costco), and/or a blend of other deeply colored organic berries. Frozen cherries, blackberries, raspberries, or goji berries are great choices.

Add 2-3 scoops of your protein powder, preferably whey isolate or brown rice protein. Add some healthy fat in the form of 1 teaspoon extra virgin olive oil, 1 teaspoon raw coconut oil, or even some avocado. Blend on HIGH for another minute. This turns your green smoothie purple, and it is loaded with rejuvenating, disease fighting anti-oxidants like anthocyanins, polyphenols, carotenoids, and flavonoids.


Repeat tomorrow morning! Mix It up with other colorful fruits and veggies!


Dr. Ryan’s Green Drink – To Your Good Health

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This nutrient and energy packed meal is the foundation for all healing and maintaining vibrant health. These whole food smoothies made by grinding the entire fruit or veggie are far superior to any kind of juicing where the fiber or pulp is separated from the juice. Grinding fresh raw greens and fruits exposes more of the plant nutrients to your digestive system for easy absorption.

Into your VitaMix Blender place:

  • 1 cored organic apple with the skin
  • 1 or 2 cored organic juicy pears with the skin
  • 1-2″ square peeled fresh organic ginger root (optional)
  • 4 ounces ice cubes, plus 8 ounces purified or spring water

Blend on HIGH for 1 minute or until it’s the consistency of applesauce. 
Add:
4 cups market fresh organic greens, any combination of:

  • black/dinosaur kale, at least 5 leaves
  • beet greens, swiss chard or collard greens, stems removed
  • spinach, parsley, or cabbage leaves
  • mustard greens or dandelion greens
  • 12 more ounces water or organic pomegranate juice
  • 5 drops clear liquid Stevia Extract (optional)

Blend on HIGH for 1 minute or until smooth.
 STORE most of this green base in a 40-ounce stainless steel bottle in the fridge.

The New Facts of Life, Part 1

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A discussion of the interrelations between food, health, and the environment is extremely topical today. In part one of this three part essay we’ll discuss Ecological Literacy.

Rising food prices together with the price of oil and a series of so-called “natural” catastrophes dominate the news every day. At the same time, there is a lot of confusion. Why are world food prices increasing so quickly and dramatically? Why is world hunger rising again after a long steady decline? What do
food prices have to do with the price of oil? Why is it so important to grow food locally and organically? In this brief talk, I shall try to show that a full understanding of these issues requires a new ecological understanding of life (a new “ecological literacy”) as well as a new kind of “systemic” thinking – thinking in terms of relationships, patterns, and context.

Indeed, over the last 25 years, such a new understanding of life has emerged at the forefront of science. I want to illustrate this new understanding by asking the age-old question, what is life? What’s the difference between a rock and a plant, animal, or microorganism? To understand the nature of life, it is not enough to understand DNA, proteins, and the other molecular structures that are the building blocks of living organisms, because these structures also exist in dead organisms, for example, in a dead piece of wood or bone.

The difference between a living organism and a dead organism lies in the basic process of life – in what sages and poets throughout the ages have called the “breath of life.” In modern scientific language, this process of life is called “metabolism.” It is the ceaseless flow of energy and matter through a network of chemical reactions, which enables a living organism to continually generate, repair, and perpetuate itself. In other words, metabolism involves the intake, digestion, and transformation of food.

Metabolism is the central characteristic of biological life. But understanding metabolism is not enough to understand life. When we study the structures, metabolic processes, and evolution of the myriads of species on the planet, we notice that the outstanding characteristic of our biosphere is that it has sustained life for billions of years. How does the Earth do that? How does nature sustain life?

Ecological literacy
To understand how nature sustains life, we need to move from biology to ecology, because sustained life is a property of an ecosystem rather than a single organism or species. Over billions of years of evolution, the Earth’s ecosystems have evolved certain principles of organization to sustain the web of life. Knowledge of these principles of organization, or principles of ecology, is what we mean by “ecological literacy.”

In the coming decades, the survival of humanity will depend on our ecological literacy – our ability to understand the basic principles of ecology and to live accordingly. This means that ecoliteracy must become a critical skill for politicians, business leaders, and professionals in all spheres, and should be the most important part of education at all levels – from primary and secondary schools to colleges, universities, and the continuing education and training of professionals.

We need to teach our children, our students, and our corporate and political leaders, the fundamental facts of life – that one species’ waste is another species’ food; that matter cycles continually through the web of life; that the energy driving the ecological cycles flows from the sun; that diversity assures resilience; that life, from its beginning more than three billion years ago, did not take over the planet by combat but by networking.

All these principles of ecology are closely interrelated. They are just different aspects of a single fundamental pattern of organization that has enabled nature to sustain life for billions of years. In a nutshell: nature sustains life by creating and nurturing communities. No individual organism can exist in isolation. Animals depend on the photosynthesis of plants for their energy needs; plants depend on the carbon dioxide produced by animals, as well as on the nitrogen fixed by bacteria at their roots; and together plants, animals, and microorganisms regulate the entire biosphere and maintain the conditions conducive to life.

Sustainability, then, is not an individual property but a property of an entire web of relationships. It always involves a whole community. This is the profound lesson we need to learn from nature. The way to sustain life is to build and nurture community. A sustainable human community interacts with other communities – human and nonhuman – in ways that enable them to live and develop according to their nature. Sustainability does not mean that things do not change. It is a dynamic process of co-evolution rather than a static state.

http://www.ecoliteracy.org/essays/new-facts-life

The New Facts of Life, Part 2

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A discussion of the interrelations between food, health, and the environment is extremely topical today. In part two of this three part essay we’ll discuss Systems Thinking.

to read part one click here

Systems thinking
The fact that ecological sustainability is a property of a web of relationships means that in order to understand it properly, in order to become ecologically literate, we need to learn how to think in terms of relationships, in terms of interconnections, patterns, context. In science, this type of thinking is known as systemic thinking or “systems thinking.” It is crucial for understanding ecology, because ecology – derived from the Greek word oikos (“household”) – is the science of relationships among the various members of the Earth Household.

Systems thinking emerged from a series of interdisciplinary dialogues among biologists, psychologists, and ecologists, in the 1920s and ’30s. In all these fields, scientists realized that a living system – organism, ecosystem, or social system – is an integrated whole whose properties cannot be reduced to those of smaller parts. The “systemic” properties are properties of the whole, which none of its parts have. So, systems thinking involves a shift of perspective from the parts to the whole. The early systems thinkers coined the phrase, “The whole is more than the sum of its parts.”

What exactly does this mean? In what sense is the whole more than the sum of its parts? The answer is: relationships. All the essential properties of a living system depend on the relationships among the system’s components. Systems thinking means thinking in terms of relationships. Understanding life requires a shift of focus from objects to relationships.

For example, each species in an ecosystem helps to sustain the entire food web. If one species is decimated by some natural catastrophe, the ecosystem will still be resilient if there are other species that can fulfill similar functions. In other words, the stability of an ecosystem depends on its biodiversity, on the complexity of its network of relationships. This is how we can understand stability and resilience by understanding the relationships within the ecosystem.

Understanding relationships is not easy for us, because it is something that goes counter to the traditional scientific enterprise in Western culture. In science, we have been told, things need to be measured and weighed. But relationships cannot be measured and weighed; relationships need to be mapped. So there is another shift: from measuring to mapping.

In biology, a recent dramatic example of this shift happened in the Human Genome Project. Scientists became acutely aware that, in order to understand the functioning of genes it is not enough to know their sequence on the DNA; we need to be able to also map their mutual relationships and interactions.

Now, when you map relationships, you will find certain configurations that occur repeatedly. This is what we call a pattern. Networks, cycles, feedback loops, are examples of patterns of organization that are characteristic of life. Systems thinking involves a shift of perspective from contents to patterns.

I also want to emphasize that mapping relationships and studying patterns is not a quantitative but a qualitative approach. Systems thinking implies a shift from quantity to quality. A pattern is not a list of numbers but a visual image.

The study of relationships concerns not only the relationships among the system’s components, but also those between the system as a whole and surrounding larger systems. Those relationships between the system and its environment are what we mean by context.

For example, the shape of a plant, or the colors of a bird, depend on their environment – on the vegetation, climate, etc. – and also on the evolutionary history of the species, on the historical context. Systems thinking is always contextual thinking. It implies a shift from objective knowledge to contextual knowledge.

Finally, we need to understand that living form is more than a shape, more than a static configuration of components in a whole. There is a continual flow of matter through a living system, while its form is maintained; there is development, and there is evolution. The understanding of living structure is inextricably linked to the understanding of metabolic and developmental processes. So, systems thinking includes a shift of emphasis from structure to process.

All these shifts of emphasis are really just different ways of saying the same thing. Systems thinking means a shift of perception from material objects and structures to the nonmaterial processes and patterns of organization that represent the very essence of life.

This essay is adapted from a speech Fritjof Capra delivered at a professional development institute, “Linking Food, Health, and the Environment,” hosted by the Center for Ecoliteracy and Teachers College Columbia University in the summer of 2008.

http://www.ecoliteracy.org/essays/new-facts-life

The New Facts of Life, Part 3

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A discussion of the interrelations between food, health, and the environment is extremely topical today. In part three of this three part essay we’ll discuss Current World Problems.

Current world problems
Once we become ecologically literate, once we understand the processes and patterns of relationships that enable ecosystems to sustain life, we will also understand the many ways in which our human civilization, especially since the Industrial Revolution, has ignored these ecological patterns and processes and has interfered with them. And we will realize that these interferences are the fundamental causes of many of our current world problems.

It is now becoming more and more evident that the major problems of our time cannot be understood in isolation. They are systemic problems, which means that they are all interconnected and interdependent. One of the most detailed and masterful documentations of the fundamental interconnectedness of world problems is the new book by Lester Brown, Plan B (Norton, 2008). Brown, founder of the Worldwatch Institute, demonstrates in this book with impeccable clarity how the vicious circle of demographic pressure and poverty leads to the depletion of resources – falling water tables, wells going dry, shrinking forests, collapsing fisheries, eroding soils, grasslands turning into desert, and so on – and how this resource depletion, exacerbated by climate change, produces failing states whose governments can no longer provide security for their citizens, some of whom in sheer desperation turn to terrorism.

Virtually all our environmental problems are threats to our food security – falling water tables; increasing conversion of cropland to non-farm uses; more extreme climate events, such as heat waves, droughts, and floods; and, most recently, increasing diversion of grains to biofuel.

A critical factor in all this is the fact that world oil production is reaching its peak. This means that, from now on, oil production will begin to decrease worldwide, extraction of the remaining oil will be more and more costly, and hence the price of oil will continue to rise. Most affected will be the oil-intensive segments of the global economy, in particular the automobile, food, and airline industries.

The search for alternative energy sources has recently led to increased production of ethanol and other biofuels, especially in the United States, Brazil, and China. And since the fuel-value of grain is higher on the markets than its food-value, more and more grain is diverted from food to producing fuels. At the same time, the price of grain is moving up toward the oil-equivalent value. This is one of the main reasons for the recent sharp rise of food prices. Another reason, of course, is that a petrochemical, mechanized, and centralized system of agriculture is highly dependent on oil and will produce more expensive food as the price of oil increases. Indeed, industrial farming uses 10 times more energy than sustainable, organic farming.

The fact that the price of grain is now keyed to the price of oil is only possible because our global economic system has no ethical dimension. In such a system, the question, “Shall we use grain to fuel cars or to feed people?” has a clear answer. The market says, “Let’s fuel the cars.”

This is even more perverse in view of the fact that 20 percent of our grain harvest will supply less than 4 percent of automotive fuel. Indeed, the entire ethanol production in this country could easily be replaced by raising average fuel efficiency by 20 percent (i.e. from 21 mpg to 25 mpg), which is nothing, given the technologies available today.

The recent sharp increase in grain prices has wreaked havoc in the world’s grain markets, and world hunger is now on the rise again after a long steady decline. In addition, increased fuel consumption accelerates global warming, which results in crop losses in heat waves that make crops wither, and from the loss of glaciers that feed rivers essential to irrigation. When we think systemically and understand how all these processes are interrelated, we realize that the vehicles we drive, and other consumer choices we make, have a major impact on the food supply to large populations in Asia and Africa.

All these problems, ultimately, must be seen as just different facets of one single crisis, which is largely a crisis of perception. It derives from the fact that most people in our society, and especially our political and corporate leaders, subscribe to the concepts of an outdated worldview, a perception of reality inadequate for dealing with our overpopulated, globally interconnected world.

The main message of Lester Brown’s Plan B, is that there are solutions to the major problems of our time; some of them even simple. But they require a radical shift in our perceptions, our thinking, our values. And, indeed, we are now at the beginning of such a fundamental change of worldview, a change of paradigms as radical as the Copernican Revolution. Systems thinking and ecological literacy are two key elements of the new paradigm, and very helpful for understanding the interconnections between food, health, and the environment, but also for understanding the profound transformation that is needed globally for humanity to survive.

This essay is adapted from a speech Fritjof Capra delivered at a professional development institute, “Linking Food, Health, and the Environment,” hosted by the Center for Ecoliteracy and Teachers College Columbia University in the summer of 2008.

http://www.ecoliteracy.org/essays/new-facts-life

TED Talk: Wade Davis, Anthropologist

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Anthropologist Wade Davis muses on the worldwide web of belief and ritual that makes us human. He shares breathtaking photos and stories of the Elder Brothers, a group of Sierra Nevada indians whose spiritual practice holds the world in balance.

A National Geographic Explorer-in-Residence, he has been described as “a rare combination of scientist, scholar, poet and passionate defender of all of life’s diversity.”