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Dave's Blog

PDGFs in Vascular Disease (with a focus on PDGF-C and PDGF-D)

A common thread in all forms of vascular disease, including cardiovascular disease, pulmonary arterial hypertension (PAH), aneurysms, and atherosclerosis, is the presence of low-grade inflammation that results in vascular and tissue remodeling. This inflammatory state arises due to infiltrating immune cells (leukocytes) and activated vascular cells such as endothelial cells (ECs), smooth muscle cells (SMCs), and adventitial fibroblasts (AFBs), all of which release growth factors and cytokines to trigger remodeling and further enhance the inflammatory state (creating a sustained feedback loop). The cause of this activation can depend on context and is for the most part, unknown. However, one of

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June 3, 2018

How PTEN May Play A Role In Vascular Disease Pathogenesis

How PTEN May Play A Role In Vascular Disease Pathogenesis Blood Vessels & Smooth Muscle Cells Vessels are the pipeline for transporting blood throughout the body. Blood, in turn, carries oxygen, nutrients, water, and other chemicals to tissues and organs throughout the body. The blood vessel is comprised of three main layers, the tunica intima, the tunica media, and the tunica adventitia. All three layers play a unique role in both physiological homeostasis and in pathological conditions. In this post, we will briefly focus on the role that the key constituents of the tunica media layer, the smooth muscle cells

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March 1, 2018

Reactive Oxygen and Nitrogen Species in Pulmonary Hypertension

  In pulmonary hypertension, there is pathological remodeling of the blood vessels due to a pathological hypertensive environment within the vasculature. This hypertensive environment influences how all cells of the vasculature (endothelial cells and smooth muscle cells), as well as fibroblasts and immune cells behave. The environment typically activates fibroblasts and immune cells, causes de-differentiation in smooth muscle cells, induces the contractile phenotype in smooth muscle cells, and may even pushes endothelial cells to failure. How this pathological hypertensive environment occurs is unknown. For example, it could arise from underlying inflammation, from hypoxia, or an apoptosis process gone haywire… There

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September 5, 2017

Antioxidants and Reactive Oxygen Species in PH – Do Antioxidants Help or Hurt PH?

While it may not be the cause, evidence from several studies that supports the fact that increased oxidative stress and reactive oxygen species (ROS) together with decreased antioxidant activity can contribute to enhanced pulmonary vasoconstriction, vascular remodeling, and right heart dysfunction in pulmonary hypertension. Despite this evidence however, it is still unknown whether or not an oxidant/antioxidant imbalance contributes directly to the development of severe PAH. Answering this question is the aim of the recent paper reviewed in today’s post by Jernigan et al., “Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension”. ROS in PH Many

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August 10, 2017

Inflammation in Pulmonary Hypertension – A Scientific Perspective, with a focus on Hypoxic PH

What is inflammation? Inflammation is a complex biological response of the body to remove foreign objects like pathogens (bacteria, virus, fungus), damaged cells, or irritants. It involves cells of the immune system, blood cells, tissue cells, and chemical mediators such as cytokines, chemokines, and reactive oxygen species. We typically have negative connotations associated with inflammation, which is justified, but not all cases of inflammation are negative. We need inflammatory processes to remove harmful pathogens, damaged cells or irritants. The problem arises when this inflammation goes unresolved, and becomes a chronic condition. There is another common harmful side of the immune

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August 8, 2017

The Cholesterol Paradox, Part 3 – LDL in Heart Disease & Pulmonary Hypertension

There is more to LDL than meets the eye… While it is true that LDL is an established marker of cardiovascular disease risk, we need to be clear just how and why exactly this is so. First things first. LDL is a means for delivering cholesterol to tissues that need it (and all cells need cholesterol to survive). Cholesterol (and thus LDL) is necessary for life: it is involved in hormone synthesis (including sex hormones), cell wall synthesis and maintenance, and the synthesis of vitamin D and bile acids. Additionally, it is involved in the process of repairing cellular injury. Now

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March 12, 2017

The Cholesterol Paradox, Part 2

This is part of a series of posts where I share and dissect information about cholesterol, the science behind cholesterol, and common fallacies surrounding cholesterol. Most of these posts are going to be short… where I just share bits of information that I’ve archived or that I’ve recently found, and some thoughts surrounding them. For Part I of this series, click here. For this post, I want to reflect on a quote from Metabolic Regulation: A Human Perspective by Keith N. Frayn (my emphasis added): “Perhaps surprisingly, the amount of cholesterol in the diet is not a major factor affecting the blood cholesterol

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February 10, 2017

Can Diet Help Improve Pulmonary Hypertension? An Insight from Inflammatory Bowel Disease Research

While reading a recent paper titled “Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications” I experienced a feeling a remarkable familiarity… I felt as if I was reading a paper about endothelial dysfunction in Pulmonary Hypertension. It appears that endothelial cell (EC) dysfunction in both inflammatory bowel disease (IBD) and pulmonary hypertension (PH) are quite similar: the same mechanisms of dysfunction abound, the same proinflammatory molecules are released. There is proliferation, smooth muscle cell tone activation, platelet aggregation, hypoxia, eNOS downregulation, imbalance between vasodilators and vasoconstrictors, etc.  Even though this kind of makes sense (that pathology in a

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January 26, 2017

“Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension” – A Review of Lipid Peroxidation in PH

A key underpinning in the pathological development of PAH is thought to be the abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs), and it is well known that oxidative stress plays a key role in this process. One oxidative stress pathway is lipid peroxidation, which has been found to contribute to abnormal PASMC growth. A major end product of lipid peroxidation processes, specifically from omega-6 peroxidation, is the compound 4-hydroxynonenal (HNE). [For those of a chemistry bent, 4-HNE is an aldehyde]. Of interest is the fact that 4-HNE has been found to contribute to PASMC growth and this compound has

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January 12, 2017

Pulmonary Edema in PH & PVOD – Potential Causes of PVOD Misdiagnosis

*DISCLAIMER: These are my own thoughts and opinions based on my research and are not meant to be taken as medical advice.* Below is a potential explanation for how edema could occur in Pulmonary Hypertension (PH) patients receiving vasodilator therapy, thus leading to them being potentially misdiagnosed for Pulmonary Veno-Occlusive Disease (PVOD)… It makes sense to think that because a PH patient does not respond to vasodilator therapy well, or experiences edema due to vasodilator therapy, it may be an indication that they have PVOD. The theory goes that vasodilators can “open” up the vasculature (even in PH patients) and

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December 31, 2016

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