Molecular Interactions of Arterial Hypertension in Its Target Organs

Abstract

Arterial hypertension (AH) is a major risk factor for the development of cardiovascular diseases. It is estimated that the disease affects between 10% and 20% of the adult population and is responsible for 5.8% of all deaths worldwide. Several pathophysiologic factors are crucial in AH, including inappropriate activation of the renin-angiotensin-aldosterone system, oxidative stress and inflammation. The heart, kidney, brain, retina and arterial blood vessels are prime targets of hypertensive damage. Uncontrolled and untreated AH accelerates the damage to these organs and could cause their failure. Damage to these organs could also manifest as coronary heart disease, cognitive impairment, retinopathy or optic neuropathy. For better understanding, it is important to analyze molecular factors which take part in pathogenesis of AH and hypertension-related target organ damage. In our paper, we would like to focus on molecular interactions of AH in the heart, blood vessels, brain and kidneys. We focus on matrix metalloproteinases, the role of immune system, the renin-angiotensin-aldosterone system and oxidative stress in hypertensive induced organ damage.

Keywords: arterial hypertension; blood pressure; matrix metalloproteinases; reactive oxygen species; renin-angiotensin-system; vascular remodeling.

Figure 1

Role of MMPs in hypertensive organ damage.

Figure 2

The role of immune cells in target organ damage. In response to hypertensive stimuli, the immune system is activated. Various immune cell subsets release pro-hypertensive molecules that promote organ damage via action in vasculature, kidneys, heart, and brain. Furthermore, the immune cells rise the BP via enhanced vasoconstriction and by that, worsen the course of AH. Abbreviations: BP-blood pressure, AH—arterial hypertension.

Figure 3

The RAAS system: the biological effects via angiotensin II-type 1 and type 2 receptors activation. Both systemically and locally produced Ang II bind to AT-1R and promote inflammation and cell death. Recent studies have shown that Ang II-induced activation of AT-2R and elicits the opposite functions to those of AT-1R. Abbreviations: Ang II-angiotensin II, AT-1R-Ang II type 1 receptor, AT-2R-Ang II type 2 receptor, ROS-reactive oxygen species.

Figure 4

Correlation and positive feedback between ROS, immune cells and hypertensive organ damage. Accumulation of ROS leads to activation of cells of the immune system and both factors lead to hypertensive organ damage. The organ damage intensifies ROS production and activates immune system.

Figure 5

The role of ERS in pathophysiology in TOD. Excessive ERS can trigger pathological changes within the cells, leading to its injury and impairment and eventually participating in the onset of development and progression of organ damage. Abbreviations: ERS-endoplasmic reticulum stress, VSMC-vascular smooth muscle cells, TOD-target organ damage.