Exploring calmodulin-related proteins, which mediate development of hypertension, in vascular tissues of spontaneous

Tatsuya Usui1, Muneyoshi Okada, Yukio Hara

  • 1Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori, Japan.

Insights

Calmodulin-related proteins are altered in hypertensive rats, suggesting their role in the development of hypertensive vascular diseases. This study investigated changes in specific proteins within blood vessels of spontaneously hypertensive rats.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Calmodulin (CaM) regulates critical cellular functions, including inflammation, apoptosis, and muscle contraction.
  • Emerging evidence links CaM-related proteins to cardiovascular diseases.
  • The specific role of CaM-related proteins in hypertensive vascular diseases remains largely unexplored.

Purpose of the Study:

  • To investigate the expression levels of six CaM-related proteins in the vascular tissues of spontaneously hypertensive rats (SHR).
  • To determine if altered expression of these proteins contributes to the pathogenesis of hypertensive vascular diseases.

Main Methods:

  • Western blotting was employed to quantify protein expression.
  • Aorta and mesenteric artery tissues were analyzed from SHR and normotensive Wistar Kyoto rats (WKY).

Main Results:

  • In the aorta of SHR, increased expression of eukaryotic elongation factor 2 kinase (eEF2K) and death-associated protein kinase (DAPK)3 was observed compared to WKY.
  • Conversely, Ca(2+)/CaM-dependent protein kinase IIδ, histone deacetylase (HDAC)4, and HDAC5 protein levels decreased in the aorta of SHR.
  • In mesenteric arteries, eEF2K, HDAC4, and DAPK3 showed increased expression, while HDAC5 decreased in SHR compared to WKY.

Conclusions:

  • Expression levels of several CaM-related proteins are significantly altered in the vascular tissues of SHR.
  • These findings suggest that CaM-related proteins play a role in the development of hypertensive vascular diseases.

Related Concept Videos

Hypertension II: Pathophysiology01:29

Hypertension II: Pathophysiology

Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...
Hypertension and Regulation of Blood Pressure01:18

Hypertension and Regulation of Blood Pressure

Hypertension, the most common cardiovascular disease, is diagnosed through repeated measurements of elevated blood pressure. Its risks, including damage to the kidney, heart, and brain, are directly proportional to blood pressure levels. Starting from 115/75 mm Hg, the risk of cardiovascular disease doubles with each increment of 20/10 mm Hg. The diagnosis relies on blood pressure measurements, not on patient symptoms, as hypertension is often asymptomatic until end-organ damage is imminent or...
Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
Neural Regulation of Blood Pressure01:18

Neural Regulation of Blood Pressure

The neural regulation of blood pressure involves intricate interactions between the autonomic nervous system (ANS) and cardiovascular system, ensuring adequate perfusion of tissues. This regulation primarily occurs through baroreceptor and chemoreceptor reflexes, involving both short-term and long-term mechanisms.
Baroreceptor Reflex
Baroreceptors, located in the carotid sinuses and aortic arch, detect changes in blood pressure. When blood pressure rises, these stretch-sensitive receptors...