Dr. Ramakrishnan studies the role of a protein pump known as Na⁺/K⁺-ATPase in macrophages, which are immune cells in the body. He investigates how this pump interacts with other proteins to facilitate the trapping and build-up of harmful cholesterol in artery walls, a process that can lead to atherosclerosis, a type of heart disease. His research aims to find ways to prevent or treat heart disease by targeting the functions of this protein pump, especially in conjunction with high-fat diets.
Key findings
Reduced function of the Na⁺/K⁺-ATPase pump in susceptible mice prevented the development of heart disease, even with a high-fat diet.
Blocking the Na⁺/K⁺-ATPase may represent a new therapeutic strategy for preventing or treating heart disease.
The interaction between oxidized LDL (a harmful form of cholesterol) and CD36 (a receptor on macrophages) is critical for cholesterol accumulation in artery walls.
Frequently asked questions
Does Dr. Ramakrishnan study heart disease?
Yes, he specifically researches the mechanisms that lead to heart disease, focusing on cholesterol accumulation in arteries.
What treatments has Dr. Ramakrishnan researched for heart disease?
He is exploring the potential of targeting the Na⁺/K⁺-ATPase protein to prevent or treat heart disease.
Is Dr. Ramakrishnan's work relevant to patients with high cholesterol?
Yes, his research directly addresses the processes involved in cholesterol accumulation, which is a key issue for individuals with high cholesterol.
Publications in plain English
A CD36 transmembrane domain peptide interrupts CD36 interactions with membrane partners on macrophages and inhibits atherogenic functions.
2023
Translational research : the journal of laboratory and clinical medicine
Huang W, Li R, Zhang J, Cheng Y, Ramakrishnan DP +1 more
Plain English This study looked at a protein called CD36 found on immune cells (macrophages) and how it interacts with other proteins on their surface to contribute to heart disease. Researchers found that a specific part of CD36 can be blocked with a synthetic peptide, which led to significant reductions in harmful processes: cells took up less oxidized LDL (a type of bad cholesterol), formed fewer foam cells (which can lead to plaque buildup), and produced less reactive oxygen species (harmful molecules). These findings are important because they suggest a way to reduce heart disease risk by targeting CD36 interactions.
Who this helps: This helps patients at risk for heart disease.
Extracellular Vesicles Activate a CD36-Dependent Signaling Pathway to Inhibit Microvascular Endothelial Cell Migration and Tube Formation.
2016
Arteriosclerosis, thrombosis, and vascular biology
Ramakrishnan DP, Hajj-Ali RA, Chen Y, Silverstein RL
Plain English This study looked at how tiny particles released by cells, called extracellular vesicles (EVs), affect the movement and growth of blood vessel cells (endothelial cells) that help form new blood vessels. The researchers found that these EVs can significantly reduce the ability of these cells to move and form new vessels by using a specific pathway linked to a protein called CD36. They saw that EVs from a variety of cell types inhibited tube formation and cell migration, showing that this is a general effect that could impact blood vessel growth in various situations.
Who this helps: This benefits patients with diseases where abnormal blood vessel growth is a problem, such as cancer or diabetic retinopathy.
LPA/PKD-1-FoxO1 Signaling Axis Mediates Endothelial Cell CD36 Transcriptional Repression and Proangiogenic and Proarteriogenic Reprogramming.
2016
Arteriosclerosis, thrombosis, and vascular biology
Ren B, Best B, Ramakrishnan DP, Walcott BP, Storz P +1 more
Plain English This study looked at how a substance called lysophosphatidic acid affects a specific receptor, CD36, in cells that line blood vessels. Researchers found that this substance reduces CD36 levels through a signaling process involving a protein called PKD-1, which leads to changes that promote blood vessel formation (angiogenesis). Specifically, when CD36 is turned off, these cells begin to produce another protein, ephrin B2, which is important for making new blood vessels, especially in conditions like cancer.
Who this helps: This information can benefit patients with cardiovascular diseases and cancer by guiding new treatment approaches.
Oxidized LDL-bound CD36 recruits an Na⁺/K⁺-ATPase-Lyn complex in macrophages that promotes atherosclerosis.
2015
Science signaling
Chen Y, Kennedy DJ, Ramakrishnan DP, Yang M, Huang W +5 more
Plain English Researchers discovered that a protein pump called Na⁺/K⁺-ATPase works together with other proteins to help immune cells called macrophages trap and accumulate harmful cholesterol in artery walls, which is the core problem in heart disease. By reducing this pump's function in mice prone to heart disease, the researchers prevented the disease from developing, even when the mice ate a high-fat diet. This suggests that blocking this pump could be a new way to prevent or treat heart disease.
Regulation of angiogenesis by phospholipid lysophosphatidic acid.
2013
Frontiers in bioscience (Landmark edition)
Chen Y, Ramakrishnan DP, Ren B
Plain English This study explored how a molecule called lysophosphatidic acid (LPA) influences the behavior of cells that line blood vessels and how new blood vessels are formed, which is essential for various health conditions. Researchers found that LPA affects key processes like cell migration and growth, highlighting its role in both normal and abnormal blood vessel formation. Understanding how LPA works could lead to better treatments for heart diseases and cancers, potentially improving patient outcomes.
Who this helps: Patients with heart disease and cancer.
Thrombospondin-1 modulates VEGF signaling via CD36 by recruiting SHP-1 to VEGFR2 complex in microvascular endothelial cells.
2013
Blood
Chu LY, Ramakrishnan DP, Silverstein RL
Plain English This study looked at how a protein called thrombospondin-1 (TSP-1) affects the signaling process of vascular endothelial growth factor (VEGF) in small blood vessel cells. The researchers found that TSP-1 interacts with another protein, CD36, which helps recruit SHP-1, a molecule that reduces VEGF signaling. This process leads to decreased activity in VEGF pathways that promote blood vessel growth, revealing a new way to potentially control blood vessel development in diseases.
Who this helps: This research benefits patients with conditions involving abnormal blood vessel growth, such as cancer or certain eye diseases.
Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress.
2006
The Journal of physiology
Kumar GK, Rai V, Sharma SD, Ramakrishnan DP, Peng YJ +2 more
Plain English This study looked at how repeated low oxygen conditions (called chronic intermittent hypoxia, or CIH) affect the adrenal glands in adult rats. The researchers found that after exposure to CIH, these glands released more stress hormones (noradrenaline and adrenaline) when faced with low oxygen, whereas normal or continuously low oxygen didn’t trigger this response. This is important because it shows a mechanism that might explain why people with conditions that involve low oxygen levels can experience high blood pressure and increased stress hormone levels.
Who this helps: This helps patients suffering from sleep apnea or other respiratory conditions that lead to intermittent low oxygen levels.