“It was found that the treatment of cultured primary human pulmonary artery smooth muscle cells (SMCs) or human pulmonary artery endothelial cells with the recombinant SARS-CoV-2 spike protein S1 subunit is sufficient to promote cell signaling without the rest of the viral components [21]. Furthermore, our analysis of the postmortem lung tissues of patients who died of COVID-19 has determined that these patients exhibited pulmonary vascular wall thickening, a hallmark of pulmonary arterial hypertension (PAH) [21]. Based on these results, we proposed that the SARS-CoV-2 spike protein (without the rest of the viral components) triggers cell signaling events that may promote pulmonary vascular remodeling and PAH as well as possibly other cardiovascular complications ... spike protein dramatically increased angiotensin II, and the angiotensin receptor inhibitor losartan attenuated the spike protein-induced enhancement of lung injury [28]. Thus, these in vivo studies demonstrated that the spike protein of SARS-CoV-1 (without the rest of the virus) reduces the ACE2 expression, increases the level of angiotensin II, and exacerbates the lung injury. The SARS-CoV-2 spike protein without the rest of the viral components has also been shown to activate cell signaling ... activated NF-κB and AP-1 transcription factors as well as p38 and ERK mitogen-activated protein kinases, releasing interleukin-6. This cell signaling cascade was found to be triggered by the SARS-CoV-2 spike protein downregulating the ACE2 protein expression, subsequently activating the angiotensin II type 1 receptor ... human cells are sensitively affected by the extracellular and/or intracellular spike proteins though the activation of cell signal transduction ... “... The increased pulmonary vascular resistance in PAH results in right heart failure and subsequently death. Patients diagnosed with PAH only live for 2–3 years from the time of diagnosis on average if untreated [30,31]. Even with currently available therapies, only 60–70% of PAH patients survive for three years”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827936/